Home Journals Articles Updates About
CN
image
收藏切换
Swarming Magnetic Fe3O4@Polydopamine-Tannic Acid Nanorobots: Integrating Antibiotic-Free Superficial Photothermal and Deep Chemical Strategies for Targeted Bacterial Elimination
收藏切换
PDF
Luying Si1, †, Shuming Zhang1, †, Huiru Guo1, Wei Luo1, 2, Yuqin Feng1, Xinkang Du1, Fangzhi Mou1, *, Huiru Ma2, 3, *, Jianguo Guan1, 2, *
Research. Vol 7 Article ID 0438
Less
收藏切换
Research. Vol 7 Article ID 0438
• Research Article •
Swarming Magnetic Fe3O4@Polydopamine-Tannic Acid Nanorobots: Integrating Antibiotic-Free Superficial Photothermal and Deep Chemical Strategies for Targeted Bacterial Elimination
Full
Luying Si1, †, Shuming Zhang1, †, Huiru Guo1, Wei Luo1, 2, Yuqin Feng1, Xinkang Du1, Fangzhi Mou1, *, Huiru Ma2, 3, *, Jianguo Guan1, 2, *
Affiliations
  • 1State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, China.
  • 2 Wuhan Institute of Photochemistry and Technology, Wuhan, China.
  • 3School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.
Published: 2024-07-31 doi: 10.34133/research.0438
Outline
收藏切换

Micro/nanorobots (MNRs) are envisioned to provide revolutionary changes to therapies for infectious diseases as they can deliver various antibacterial agents or energies to many hard-to-reach infection sites. However, existing MNRs face substantial challenges in addressing complex infections that progress from superficial to deep tissues. Here, we develop swarming magnetic Fe3O4@polydopamine-tannic acid nanorobots (Fe3O4@PDA-TA NRs) capable of performing targeted bacteria elimination in complicated bacterial infections by integrating superficial photothermal and deep chemical strategies. The Fe3O4@PDA-TA nanoparticles (NPs), serving as building blocks of the nanorobots, are fabricated by in situ polymerization of dopamine followed by TA adhesion. When driven by alternating magnetic fields, Fe3O4@PDA-TA NPs can assemble into large energetic microswarms continuously flowing forward with tunable velocity. Thus, the swarming Fe3O4@PDA-TA NRs can be navigated to achieve rapid broad coverage of a targeted superficial area from a distance and rapidly eradicate bacteria residing there upon exposure to near-infrared (NIR) light due to their efficient photothermal conversion. Additionally, they can concentrate at deep infection sites by traversing through confined, narrow, and tortuous passages, exerting sustained antibacterial action through their surface TA-induced easy cell adhesion and subsequent membrane destruction. Therefore, the swarming Fe3O4@PDA-TA NRs show great potential for addressing complex superficial-to-deep infections. This study may inspire the development of future therapeutic microsystems for various diseases with multifunction synergies, task flexibility, and high efficiency.

Luying Si, Shuming Zhang, Huiru Guo, Wei Luo, Yuqin Feng, Xinkang Du, Fangzhi Mou, Huiru Ma, Jianguo Guan. Swarming Magnetic Fe3O4@Polydopamine-Tannic Acid Nanorobots: Integrating Antibiotic-Free Superficial Photothermal and Deep Chemical Strategies for Targeted Bacterial Elimination[J]. Research, 2024 , 7 (7) : 0438 . DOI: 10.34133/research.0438
Full Text
Less
Introduction
Less
Bacterial infections are one of the main causes of worldwide morbidity and death [1]. Using antibiotics is considered an efficient sterilization technology, but excessive use will increase antimicrobial resistance (AMR) and threaten human health [2]. Therefore, it is of great significance to develop non-antibiotic antimicrobial strategies [3,4]. As alternatives to antibiotics, antimicrobial peptides (AMPs) exhibiting membrane disruption and immunomodulatory ability have been developed as a common and effective strategy [5]. In addition, engineered phage, specific vaccines and quorum sensing (QS) inhibitors have been exploited to assist antibiotic therapy [6]. Unsatisfactorily, these biological agents are limited by high cost and usually show their effect only on specific infection strains. Furthermore, chemical dynamic therapy (CDT) [7], photothermal therapy (PTT) [8], photodynamic therapy (PDT) [9], and sonodynamic therapy (SDT) [10] are novel therapeutic strategies in fighting against multidrug-resistant (MDR) bacteria. As generally acknowledged, PTT is a promising physical therapy with low invasion and independence on the local concentration of chemicals in infection microenvironments. Among various photothermal agent (PTA), polydopamine (PDA) has been used as a biocompatible platform benefiting from its broad-band light absorption properties and great flexibility to be modified and incorporated with other antibacterial and anticancer agents [11–14]. Additionally, natural antibacterial-active agents including polysaccharides (e.g., chitosan) and small antibacterial molecules (e.g., polyphenols) show great potential in trauma-related infections [15,16]. Among them, tannic acid (TA) shows inherent broad-spectrum antibacterial activity and has been widely used in antibacterial materials by incorporating with hydrogels [17,18] or serving as chelating agents in metal polyphenol networks (MPNs) [19,20]. However, PTT efficacy is often limited in superficial tissue because of the limited penetration depth of light in tissues (e.g., ~1 cm for 808-nm near-infrared [NIR] light [21]). Natural antibacterial polyphenols as chemo-pharmaceuticals, on the other hand, hold promise for deep tissue treatment, but effectively delivering these molecules with high targeting efficiency remains a significant challenge.
Micro/nanorobots (MNRs) are micro/nanoscale machines capable of propelling in liquid media by harvesting energies from surrounding chemical fuels or external fields [22,23]. Benefitting from their small sizes and motility, they are expected to navigate in many hard-to-reach narrow biological environments to perform designated biomedical tasks, and thus may provide revolutionary changes to microsurgery, disease diagnosis, medical imaging, and targeted therapy [24–26]. As the collective of single MNRs, the MNR swarms show emerging collective behaviors that individual robots lack, such as powerful thrust, high robustness, dynamic reconfigurations, high imaging contrast, and collective intelligence [27–32]. Especially, the swarming magnetic nanorobots exhibit high biocompatibility and excellent adaptability to biological environments due to their fuel-free propulsion and high ion tolerance [33–40]. Thus, they show great promise in targeted eliminations of bacteria in medical catheters, root canals, biliary stents, tympanostomy tubes, and superficial wounds through mechanical destruction, magnetothermal effects, antibiotics delivery, catalytic generation of reactive oxygen species (ROS), and synergistic combinations thereof [41–47]. Nevertheless, these magnetic nanorobots are mainly designed to eliminate bacteria or biofilms on the surface of medical devices and implants or in superficial wounds, and may not be applicable in complicated bacterial infection scenarios involving both superficial and deep-seated tissues.
Here, we propose a simple design of swarming magnetic nanorobots integrating antibiotic-free superficial photothermal and deep chemical antibacterial activities (Fig. 1). The building blocks of the swarming magnetic nanorobots are designed as Fe3O4 nanoparticles coated with PTA PDA and natural antibacterial agent TA (Fe3O4@PDA-TA NPs). When actuated by an alternating magnetic field, such as rotating (Hr(t)) or precessing magnetic field (Hp(t)), Fe3O4@PDA-TA NPs self-assemble into rolling or wobbling nanochains (i.e., nanorobots) that translate in close proximity to the substrate utilizing local shear gradients [48]. Under local hydrodynamic interactions, these Fe3O4@PDA-TA NRs further organize into large microswarms while rotating around their center of mass [49]. With the powerful collective motion, the microswarm can continuously flow forward to cover a targeted area with bacterial infections from a distance and even penetrate and enter confined, narrow infection sites within deep tissues. Subsequently, they can perform superficial photothermal and deep chemical bacterial elimination simultaneously or sequentially. Specifically, Fe3O4@PDA-TA NRs covering the target area, upon exposure to NIR light, can be triggered to perform localized photothermal ablation, rapidly eradicating bacteria residing on the surface of the infection site. Meanwhile, within deep-seated infection sites, despite the hindered photothermal efficacy due to limited penetration or significant attenuation of NIR light, Fe3O4@PDA-TA NRs can exert sustained antibacterial action through their inherent chemical activities. This means that Fe3O4@PDA-TA NRs, with integrated swarming motions, photothermal conversion, and chemical antibacterial effect, show great potential to treat complicated infection lesions involving both superficial and deep-seated infection sites, such as surgical site, trauma wound, deep burn, and lung infections.
Results
Less
Fabrication and characterization of building blocks
The Fe3O4@PDA-TA NPs, as building blocks of the nanorobots, were fabricated via a simple 2-step method (Fig. 2A). The first step was to coat a PDA shell on Fe3O4@polyvinyl pyrrolidone (Fe3O4@PVP) NPs via in situ polymerization of dopamine (DA) molecules concentrated around the core, relying on the complexation between Fe (III) on the Fe3O4 core and the catechol groups of DA, along with hydrogen bonding between the carbonyl groups of PVP and the phenolic hydroxyl groups of DA (inset I in Fig. 2A). The second step involved surface modification of the intermediate Fe3O4@PDA NPs with TA to create Fe3O4@PDA-TA NPs utilizing π–π stacking and hydrogen bonding interactions between TA and the PDA layer (inset II in Fig. 2A) [20,50]. Figure 2B shows scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of Fe3O4@PVP, Fe3O4@PDA, and Fe3O4@PDA-TA NPs. Compared with the pristine Fe3O4@PVP NPs (Fig. 2Bi and iv), Fe3O4@PDA NPs have a smoother surface and an obvious core-shell structure, suggesting that a complete shell was formed on the Fe3O4 core (Fig. 2Bii and v). On the other hand, the obtained Fe3O4@PDA-TA NPs share a similar morphology and core-shell structure with Fe3O4@PDA NPs (Fig. 2Biii and vi). The successful coating of the PDA shell on Fe3O4@PVP NPs was confirmed by the emerging characteristic absorption band of the benzene ring skeleton at 1,486 cm−1 in the Fourier transform infrared (FT-IR) spectrum of Fe3O4@PDA NPs. In addition, the successful modification of TA onto Fe3O4@PDA NPs can be verified by the newly formed asymmetric stretching vibration (νas) and symmetric stretching vibration (νs) of C–O–C bonds at 1,212 and 1,156 cm−1, respectively, in the FT-IR spectrum of Fe3O4@PDA-TA NPs (Fig. 2C). Zeta potential (ζ) tests revealed that Fe3O4@PDA-TA NPs gained an enhanced electronegativity (ζ = −25.40 mV) after PDA coating and TA modification, attributed to the abundant surface phenolic hydroxyl groups (Fig. S1A). Thermogravimetry (TG) analysis confirmed that the mass content of PDA and TA in Fe3O4@PDA-TA NPs were 8.8 and 1.35 wt %, respectively (Fig. S1B). The statistical results indicated that, due to the PDA coating and TA modification, the average size of Fe3O4@PVP, Fe3O4@PDA, and Fe3O4@PDA-TA NPs gradually increased from 155.8 and 171.4 nm to 179.6 nm in dry state (Fig. S2). When suspended in water, their hydrodynamic sizes further increased to 217.9, 233.7, and 297.9 nm, correspondingly (Fig. S3).
X-ray photoelectron spectroscopy (XPS) spectra (Fig. 2D) and the high-resolution deconvoluted spectrum of N 1s (Fig. 2E), C 1s, and O 1s (Fig. S4) demonstrated the presence of Fe, C, N, and O elements in Fe3O4@PDA-TA NPs. The deconvoluted spectrum of N 1s in Fig. 2E revealed the C–NH2 (401.9 eV), C–NH–C (400.9 eV) and C=N (398.3 eV) bonds in Fe3O4@PDA-TA NPs, which were attributed to the PDA, and Schiff base reaction between carbonyl (C=O) groups of PVP from uncoated particle and primary amine (–NH2) groups of DA, while in Fe3O4@PVP NPs there only emerged tertiary nitrogen atoms (399.8 eV). Further, the increased peak intensity of C–N (285.9 eV) in the deconvoluted C 1s spectrum (Fig. S4A) and C–O (532.9 eV) in deconvoluted O 1s spectrum (Fig. S4B) and the decreased peak intensity of Fe–O (529.8 eV) (Fig. S4B) verified the increasing organic content of Fe3O4@PDA-TA NPs compared with Fe3O4@PVP NPs. In addition, the quantified atom content variation confirmed the enhanced mass ratio of C and O elements compared to the Fe element. For example, the C/Fe ratio elevated from 4.72 to 53.38 and the O/Fe ratio increased from 2.79 to 12.08 (Table S1), in consistence with the sharp reduction in the intensity of Fe 2p peak of Fe3O4@PDA-TA NPs in Fig. 2D.
The magnetic hysteresis loop (Fig. 2F) reveals a mass saturation magnetization (Ms) of 39.7 emu g−1 for Fe3O4@PDA-TA NPs, which is slightly lower than pristine Fe3O4@PVP NPs (44.8 emu g−1) and the intermediate product of Fe3O4@PDA NPs (40.1 emu g−1). In addition, the negligible remanent magnetization and coercivity (inset in Fig. 2F) suggest that Fe3O4@PVP, Fe3O4@PDA, and Fe3O4@PDA-TA NPs all possessed a superparamagnetic property. Like Fe3O4@PVP NPs, the prepared Fe3O4@PDA and Fe3O4@PDA-TA colloidal NPs can self-assemble into periodic nanochains exhibiting bright structural colors [51], suggesting that they had monodispersed size and robust interparticle repulsion preventing them from clumping under the magnetic field (Fig. S5). With the decreasing magnetic field strength, the structural color (Fig. S5A) and reflection peaks (Fig. S5B) of aqueous suspensions of Fe3O4@PVP, Fe3O4@PDA, and Fe3O4@PDA-TA NPs redshift gradually due to the increasing interparticle distance (i.e., lattice constant).
Magnetically driven swarming motions
As is known, superparamagnetic nanoparticles can easily be magnetized and self-assemble into nanoparticle chains due to the dipole–dipole interactions along a static magnetic field H (Fig. 3Ai). When a rotating magnetic field Hr(t) (Eq. 1) was applied, the self-assembled nanochains experienced a magnetic torque and were forced to rotate around its short axis, while 2 ends of the nanochains rotated around the precession axis when a precessing magnetic field Hp(t) (Eq. 2) was applied [33,52].
Hrt=H0cos2πftex+sin2πftez
Hpt=H0ey+H0cos2πftex+sin2πftez
Here, H0 is the amplitude of the rotating and precessing magnetic field, respectively. f is the alternating frequency; t denotes the time; and ex, ey, and ez are the unit vector along the x, y, and z axes, respectively. When the nanochains were rotating or precessing near a substrate, the top and bottom of the nanochains experienced different viscous fluidic drag forces because of local shear gradients. As a result, the hydrodynamic symmetry of the rotating or precessing nanochains was broken, and they can thus perform a “rolling” (Fig. 3Aii) or “crawling” translational motion (Fig. 3Aiii) [48]. Further, the “rolling” and “crawling” nanochains can generate a small local vortex with a flow velocity decaying as r−2, where r is the distance to its rotation axis. When they were in a crowded state, neighboring rollers were attracted and advected by one another via hydrodynamic coupling and further gathered into large compact swarms rotating around their center of mass and translating along the substrate [39,49].
The magnetic assembly, rolling, and crawling motions of single Fe3O4@PDA-TA NRs are shown in Fig. 3B and Movie S1. Under a static magnetic field (15 mT), dispersed Fe3O4@PDA-TA NPs assemble into nanoparticle chains with a wide length range from 6.0 to 20.2 μm (Fig. 3B, 0 s–25 s). Despite serious disturbance from Brownian randomization, these nanochains (i.e., single Fe3O4@PDA-TA NRs) can perform a rolling motion near the substrate when Hr(t) was applied (Fig. 3B, 45 s–78 s) and further move in a crawling mode under Hp(t) (Fig. 3B, 140 s). Notably, the nanochains dynamically merge and break when moving (Fig. 3C), and can disassemble completely back into dispersed nanoparticles upon the cessation of the magnetic field (Fig. 3B, 169 s). At a high number density, Fe3O4@PDA-TA NPs can form into cohesive swarms that continuously flow forward in rolling and crawling modes under Hr(t) and Hp(t), respectively (Fig. 3D and E and Movie S2). Nonetheless, the formed swarms present an obvious difference in collective structures. Specifically, the rolling Fe3O4@PDA-TA NRs formed into a swarm with clear density variations, featuring multiple dark stripes (or standing vortex) with concentrated nanorobots, interspersed with lighter regions exhibiting sparser distributions (Fig. 3D). In contrast, the crawling nanorobots assembled into a cloud-like swarm covering a larger area with less variation in density distribution (Fig. 3E). Therefore, during task execution, the rolling swarms may be activated to navigate through narrow channels, and the crawling motion mode was subsequently engaged as they approached the destination, enabling the swarm to swiftly and efficiently achieve broad coverage of the targeted area, facilitating subsequent therapeutic tasks.
Manipulating the applied Hr(t) or Hp(t) can adjust the collective motions of swarming Fe3O4@PDA-TA NRs. As depicted in Fig. 3F, when the magnetic field strength (H0) was kept at 25 mT, the collective velocity (U) of the nanorobots adopting whether a rolling or crawling motion mode under Hr(t) (red line in Fig. 3F) or Hp(t) (blue line in Fig. 3F) shows an increasing and then decreasing trend with the increasing f from 1 to 12 Hz. This is because the angular velocity ω of the rolling or precessing nanorobots gradually increased with the increasing f, allowing them to move more quickly on the substrate and create a stronger flow field. When f exceeded the critical values, which was the step-out frequency (fc), the rolling or precessing nanochains in the swarms gradually desynchronize with the external Hr(t) or Hp(t), resulting in a gradual decrease in U. The results in Fig. 3F suggest that the rolling swarm reaches its peak velocity of 142 μm s−1 at an fc of 8 Hz, and the crawling swarm shows a maximum U of about 174 μm s−1 at an fc of 6 Hz. Additionally, the effect of H0 on U of the swarms was also investigated (Fig. 3G). For the swarming Fe3O4@PDA-TA NRs in a rolling mode, their collective translational velocity U at a fixed f of 8 Hz increased with the increasing H0 until a critical strength of 18 mT was reached (red curve in Fig. 3G). When H0 exceeded this critical strength, U almost stabilized at ~150 μm s−1, indicating that the nanorobots overcame the viscous drag from the fluid and rotated synchronously with the applied Hr(t). Similarly, U of crawling Fe3O4@PDA-TA NRs swarm under Hp(t) with a fixed f of 6 Hz increased with the increasing H0 and reached its maximum of 178 μm s−1 when H0 exceeded 23 mT (blue curve in Fig. 3G). The above results indicate that the crawling swarm had a higher maximum mobility than the rolling one. This difference can be attributed to the less moment of inertia in the “crawling” mode, leading to the less energy required for the precessing nanorobots to rotate and move in the liquid medium. Under dark-field microscopy, the flowing swarm of Fe3O4@PDA-TA NRs displayed a bright red structural color (Fig. S6 and Movie S3). This observation confirmed their high stability during collective motion, as random aggregation would disrupt the ordered arrangement necessary for this structural color to appear.
Targeted photothermal bacterial elimination
To explore the potential of the nanorobots in the superficial photothermal bacterial elimination, the light absorption properties and photothermal effect of Fe3O4@PDA-TA NPs were tested at first. As shown in Fig. S7A, Fe3O4@PVP, Fe3O4@PDA, and Fe3O4@PDA-TA NPs all have a high dispersity in water even after the application of a high-strength H (1,000 Gs). Notably, the Fe3O4@PDA NP and Fe3O4@PDA-TA NP suspensions (125 μg ml−1) exhibit a darker color (Fig. S7A) and higher light absorption at 808 nm (Fig. S7B) compared to Fe3O4@PVP NPs. Further, the minimal difference in light absorption between Fe3O4@PDA and Fe3O4@PDA-TA suspensions suggests that PDA primarily contributes to enhanced light absorption, with minimal influence from the TA modification. The photothermal conversion ability of Fe3O4@PDA-TA, Fe3O4@PDA, and Fe3O4@PVP NPs was further investigated, as indicated by Fig. S7C and D and Table S2. The photothermal conversion efficiency (η) of Fe3O4@PDA and Fe3O4@PDA-TA NPs increased to 42.0% and 42.5%, respectively, compared to18.1% for Fe3O4@PVP NPs. As recorded by the infrared thermography (Fig. 4A), the temperature of Fe3O4@PDA-TA NPs aqueous suspension rapidly increased up to 68.2°C after irradiation for 600 s with an 808-nm laser at a power density (I) of 1.0 W cm−2. The photothermal heating curves indicate that, under the same NIR irradiation conditions, different from the negligible temperature rise of the deionized (DI) water (control group), the Fe3O4@PVP NP suspension was heated from 22 to 42°C owing to photothermal conversion of the Fe3O4 component [53]. Notably, the Fe3O4@PDA and Fe3O4@PDA-TA NP suspensions exhibit nearly identical heating curves, reaching even higher temperatures of 67.2 and 68.2°C within 600 s, respectively (Fig. 4B). This result suggests that Fe3O4@PDA-TA NPs exhibited a strong photothermal effect, and their photothermal conversion mainly came from the combined contributions of the PDA shell and the inner Fe3O4 core. In addition, Fe3O4@PDA-TA NPs demonstrate excellent repeatability and stability in photothermal conversions, as evidenced by their cycling photothermal heating–cooling curves in Fig. 4C.
The influence of NIR laser power density I and nanoparticle concentration (Cp) on the photothermal conversion of Fe3O4@PDA-TA NPs was further explored (Fig. S8). As shown in Fig. S8A, the increasing I results in steeper photothermal heating curves, and the temperature of the aqueous suspension of Fe3O4@PDA-TA NPs (250 μg ml−1) reaches 43.7, 49.6, 68.2, 74.7, and 85.8°C after NIR irradiation for 600 s at an I of 0.33, 0.5, 1.0, 1.5, and 2.0 W cm−2, respectively. Similarly, the increasing Cp leads to a higher heat rate of the aqueous Fe3O4@PDA-TA NP suspension under NIR irradiation (I = 1.0 W cm−2). For instance, it only took 100 and 80 s for the Fe3O4@PDA-TA NP suspension to reach a temperature higher than 50°C when Cp was 500 and 1,000 μg ml−1, respectively. In addition, with Cp increasing from 125, 250, and 500 to 1,000 μg ml−1, the final temperature of the aqueous suspensions after the NIR irradiation for 600 s rose from 56.7, 68.2, and 77.8 to 79.3°C, respectively (Fig. S8B). Notably, the optimal conditions for Fe3O4@PDA-TA NRs to perform photothermal bacterial elimination were found to be at a Cp of 250 μg ml−1 and an I below 1.0 W cm−2, as the final temperature of the suspension is in a mild hyperthermia range (<70°C), which can reduce the potential cytotoxicity of high-concentration nanoparticles and the hyperthermia damage of intense laser irradiation to normal tissues. Interestingly, magnetically assembled Fe3O4@PDA-TA NPs exhibited superior photothermal performance compared to their dispersed counterparts (Fig. S9). Suspensions containing assembled Fe3O4@PDA-TA NPs displayed consistently higher heating rates under a magnetic field of 200 Gs across a wide range of Cp from 125 to 1,000 μg ml−1, compared to their dispersed counterparts. This enhanced photothermal effect resulted in a final temperature difference of 5.5, 3.2, 1.6, and 1.2°C between the assembled and dispersed suspensions within 600 s at Cp of 125, 250, 500, and 1,000 μg ml−1, respectively. These findings suggest that the condensed local particle density achieved through magnetic assembly enhances the photothermal heating capacity, particularly at lower concentrations.
Benefitting from high photothermal performance and swarming motions, Fe3O4@PDA-TA NRs are envisioned to realize photothermal elimination of bacteria in a motile-targeting manner. To verify this, we used a piece of agar gel with inoculated bacteria Staphylococcus aureus colonies on its surface as a simulated superficial infection site, and the agar gel was put in the right pool of a microfluidic channel to serve as the target (Fig. 4D). For effective photothermal bacterial elimination at a remote superficial infection site, the swarming Fe3O4@PDA-TA NRs need to achieve wide-range coverage of the site from a distance before performing efficient elimination. When driven by Hr(t) with H0 of 20 mT and an f of 3 Hz, a swarm of Fe3O4@PDA-TA NRs was activated to pass through the middle canal, and reached the right pool with the target in a rolling mode (0 to 48 s in Fig. 4E). Upon arriving at the right pool, the Fe3O4@PDA-TA swarm was adjusted into a relatively widespread state (i.e., crawling mode) by switching the driving magnetic field from a rolling Hr(t) to a precessing Hp(t). In this crawling mode, the swarming Fe3O4@PDA-TA NRs could climb up the bacterial-inoculated agar gel target and cover the bacteria colonies (57 to 155 s in Fig. 4E). Then, a beam of NIR light was locally applied to activate the photothermal conversion of Fe3O4@PDA-TA NRs, generating hyperthermia to eradicate bacteria in the target area (corresponding to 190 s in Fig. 4E and Movie S4).
To investigate the antibacterial effect of Fe3O4@PDA-TA NRs in photothermal treatment, S. aureus bacteria were subjected to different experimental conditions, including pure NIR light exposure (1.0 W cm−2, NIR group), the employment of Fe3O4@PDA-TA NRs (Cp = 250 μg ml−1), and NIR irradiation at different I of 0.33, 0.5, and 1.0 W cm−2 (NRs + NIR groups). In the NRs + NIR groups, Fe3O4@PDA-TA NPs were mixed with S. aureus bacteria before being irradiated by the NIR laser at different I for 10 min, and then incubated on agar plate for colony-forming unit (CFU) counts. Meanwhile, the antibacterial experiment without nanoparticles or NIR irradiation was used as a control group. The results are shown in Fig. 4F. The agar plate is almost covered with S. aureus colonies in the NIR group, and the survival rate reaches 78.4%. In contrast, for the bacteria treated by Fe3O4@PDA-TA NPs and NIR irradiation, the numbers of S. aureus colonies observed on the agar plate reduce with the increasing I, and the survival rate decrease to 62.6%, 10.6%, and even 0.2% accompanying with an I increased from 0.33 and 0.5 to 1.0 W cm−2, respectively. The good photothermal sterilization capacity of swarming Fe3O4@PDA-TA NRs can also be verified by the fluorescence images of S. aureus under different experimental conditions (Fig. 4G). In order to distinguish, the live S. aureus bacteria were dyed green, and the dead one was dyed red. S. aureus kept alive and almost no dead S. aureus were found in the control group and the NIR group, indicating that the NIR irradiation alone had a minimal capacity to cause S. aureus apoptosis. In contrast, dead S. aureus bacteria were observed in NRs + NIR groups even at a weak I of 0.33 W cm−2. When I was increased to 0.5 W cm−2, most S. aureus were dead, and especially, almost no alive S. aureus appeared in the NRs + NIR group with an I of 1.0 W cm−2. The above results indicate that Fe3O4@PDA-TA NRs show a great potential to cover a targeted infection area from a distance via their controllable swarming motions and then rapidly eradicate bacteria residing on the infection site in virtue of their high photothermal performance.
Targeted chemical bacterial elimination
Besides the capacity to execute superficial photothermal bacterial elimination, Fe3O4@PDA-TA NRs show great potential to actively eliminate bacteria located within deep-seated infection sites utilizing their chemical antibacterial effects. For nanorobots to eliminate bacteria in a deep-seated site, they must first navigate through tortuous and narrow passages to reach the target site. If NIR light cannot be directly applied from all angles or delivered through a fiber optic source at these deep locations, the nanorobots must rely solely on their inherent chemical properties to kill bacteria in these areas. To verify this, a deep-seated infection site, simulated by a piece of agar gel with grown S. aureus colonies, was placed at the far end of a zigzag microtube with a narrow neck (inner diameter: ~400 μm) (Fig. 5A). As demonstrated by Fig. 5B and Movie S5, the swarming Fe3O4@PDA-TA NRs can smoothly traverse the zigzag microtube under the navigation of the rotating Hr(t) with adjustable orientations (0 to 220 s in Fig. 5B). Upon approaching the target, the rotating Hr(t) was switched into a precessing Hp(t) (220 s in Fig. 5B) and Fe3O4@PDA-TA NRs can further delve deeper into the target through branching narrow ravines (down to 30 μm wide) and gradually distribute themselves around the bacterial colonies (220 to 275 s in Fig. 5B). This result suggests that the swarming Fe3O4@PDA-TA NRs can travel a long distance and transverse narrow passages with varying sizes to target the deep-seated bacteria, laying the groundwork for deep antibacterial treatment.
The chemical antibacterial activity of Fe3O4@PDA-TA NRs primarily originates from their surface TA molecules. Specifically, due to abundant phenolic hydroxyl groups from surface TA molecules, Fe3O4@PDA-TA NPs (i.e., building blocks of nanorobots) exhibit excellent adhesion to the bacteria membrane owing to their easy association with the peptidoglycan, lipopolysaccharide, teichoic acid, protein, and lipid on the bacterial membrane [54]. Upon membrane adhesion, Fe3O4@PDA-TA NPs can cause cell membrane destruction and exudation of cell contents [55]. As verified by Fig. 5C, in contrast to smooth and spherical normal S. aureus cells (control group), the cell with attached Fe3O4@PDA-TA NPs displayed collapsed and wrinkled surface morphology. To evaluate the chemical antibacterial efficacy, the dose-dependent cytotoxicity of Fe3O4@PDA-TA NPs to S. aureus cells was quantitatively evaluated (Fig. 5D and E). As expected, the viability of S. aureus cells remained relatively high (>69%) when exposed to Fe3O4@PVP NPs over a wide range of concentrations. In contrast, the cell viability decreased from 26.5% to 10.3% as the concentration of Fe3O4@PDA-TA NPs increased from 31.25 to 250 μg ml−1. Surprisingly, Fe3O4@PDA NPs also have excellent chemical antibacterial efficacy. This is attributed to the abundant hydroxyl groups on the surfaces of both nanoparticles, likely leading to a shared contact-active antibacterial mechanism [56]. The Fe3O4@PDA-TA NPs have a higher antibacterial efficacy than Fe3O4@PDA NPs at equivalent concentrations (e.g., 10.3% versus 23.0% cell viability at 250 μg ml−1), although the former may experience partial detachment of surface-bound TA molecules (29.4% within 12 h) (Fig. S10). The observed mild antibacterial effect of Fe3O4@PVP NPs may come from the release of Fe2+ ions that generate ROS in the bacterial environment [42,57]. The high chemical antibacterial efficacy of Fe3O4@PDA-TA NPs was also confirmed by fluorescence microscopic images of dead (red) and surviving (green) S. aureus cells after treatment (Fig. 5F). Due to the high chemical antibacterial activity of Fe3O4@PDA and Fe3O4@PDA-TA NPs, most S. aureus cells were killed within 24 h. In contrast, minimal cell death was observed when the S. aureus cells were exposed to Fe3O4@PVP NPs and no cell death was detected with DI water (Control group). To further verify the antibacterial mechanism, the bacteria after different treatments were stained using the cell membrane permeability indicator Rhodanmine123, of which the fluorescence intensity is positively correlated with membrane potential and inversely correlated with the membrane permeability [58]. The Fe3O4@PDA-TA group exhibited the weakest fluorescence intensity, indicating that Fe3O4@PDA-TA NPs were most effective at disrupting the cell membranes of S. aureus bacteria compared to Fe3O4@PVP and Fe3O4@PDA NPs (Fig. 5G). These results revealed that the swarming Fe3O4@PDA-TA NRs can actively target bacteria in remote and narrow deep-seated sites and exert sustained chemical antibacterial effects. With combined antibiotic-free photothermal and chemical antibacterial activities, Fe3O4@PDA-TA NRs show great potential to treat complicated infection lesions involving both superficial and deep-seated infection sites.
Discussion
Less
Bacterial infections that spread from the surface to deep sites are a frequent complication in various situations, including surgical sites, traumatic wounds, deep burns, and lung infections [59,60]. For example, in ventilator-associated pneumonia (VAP), a prevalent complication in intensive care unit (ICU) patients, bacteria can infiltrate the lower respiratory tract, spreading from the bronchi and bronchioles to the alveoli. Systemic antibiotic administration is occasionally proved inefficient or ineffective, particularly against MDR and extensively drug-resistant (XDR) bacteria. Benefitting from their small sizes and motility, MNRs are expected to deliver various antibacterial agents or energies to many hard-to-reach infection sites with a high targeting efficiency, and thus may provide revolutionary changes to infection treatment [39,41–45]. However, it is of great challenge for the so-far developed MNRs to effectively manage complicated superficial-to-deep bacterial infections. In this work, we demonstrate that the swarming Fe3O4@PDA-TA NRs incorporated with photothermal and natural antibacterial agents can perform targeted bacteria elimination in complicated bacterial infection scenarios involving both superficial and deep-seated sites.
The swarming magnetic nanorobots with integrated superficial photothermal and deep chemical strategies for targeted bacterial elimination represent a significant advancement in the field of nanomedicine and micro/nanorobotics. At first, the swarming behavior of Fe3O4@PDA-TA NRs offers distinct advantages for targeted delivery and distribution within complex infection environments. Their rolling and crawling collective motions enable them to cohesively approach and rapidly achieve broad coverage of a targeted superficial area in open spaces. This facilitates subsequent uniform photothermal energy distribution and efficient eradication of surface-residing bacteria across a wide area. When facing a deep-seated infection scenario, they can navigate through confined, narrow, and tortuous passages, and actively concentrate at the deep infection site to enhance the overall efficacy of the treatment while minimizing potential off-target effects. In stark contrast, passive antibacterial nanoagents and single MNRs generally suffer from limited target coverage and slow accumulation time at the superficial infection sites, and also cannot effectively penetrate into deep-seated infection sites for bacterial eradication [46,61]. Second, by incorporating photothermal and natural antibacterial agents, the swarming Fe3O4@PDA-TA NRs can effectively combat bacterial infections with high precision, enhanced efficiency, and task flexibility. Specifically, together with wide surface coverage and deep penetration through narrow cavities, the swarming Fe3O4@PDA-TA NRs not only can rapidly eradicate bacteria residing on the superficial infection site through localized photothermal ablation but also exert sustained antibacterial action in the deep infection site through their inherent chemical activities. In contrast, those magnetic MNRs relying on single-mode physical (e.g., mechanical force and photothermal hyperthermia) or chemical antibacterial strategy (e.g., antibiotic drugs and ROS/nitric oxide generation) usually suffer from limited applicability or low bacterial elimination efficiency [43,62–64]. While some studies have reported MNRs integrating physical and chemical sterilization, they typically involve large microrobots (tens of micrometers) with catalytic properties or loaded antibiotics [42,65,66]. These approaches often require external chemicals (e.g., H2O2), have limited access to narrow cavities, raise biosafety concerns, and may be susceptible to AMR.
Several challenges and limitations must be addressed to fully realize the clinical potential of this technology. A crucial aspect is ensuring the in vivo biocompatibility and safety of Fe3O4@PDA-TA NRs. While their constituent materials (Fe3O4 NPs, PDA, and TA) have been reported to possess biocompatibility [67,68], further investigations are necessary to evaluate their biodegradability, long-term effects, and potential immunogenicity within biological systems. Additionally, further improvements in the antibacterial efficacy of Fe3O4@PDA-TA NRs are desirable. Potential strategies include incorporating additional functionalities into the building blocks, such as extra chemotactic engines to allow autonomous bacterial targeting, surface nanospikes to facilitate membrane disruption, or co-encapsulation of antibacterial agents (e.g., antibiotics, AMPs, enzymes, or immunomodulatory drugs) [69–71]. Envisioning widespread clinical use, future endeavors should prioritize the scalability and cost-effectiveness of Fe3O4@PDA-TA NPs production methods. Additionally, it is of immense promise to expand the functionalities of these swarming magnetic nanorobots for broader therapeutic applications beyond bacterial elimination. For instance, incorporating antitumor or thermolytic drugs to the building blocks of the nanorobots could enable them to realize multimodal tumor therapies and thrombosis dissolution [48,72].
In summary, we have designed swarming multifunctional magnetic Fe3O4@PDA-TA NRs that can achieve superficial photothermal and deep chemical bacterial elimination. The Fe3O4@PDA-TA NPs (building blocks) are successfully fabricated by introducing a photothermal-conversion PDA layer onto the superparamagnetic Fe3O4 core and an inherent antibacterial layer of natural product TA on the outermost shell through a simple 2-step method. They show a superparamagnetic property with a high Ms of 39.7 emu g−1 and an efficient photothermal conversion with a η of 42.54%. Under navigation of rotating Hr(t) and precessing Hp(t), Fe3O4@PDA-TA NPs can assemble into rolling or wobbling nanochains and further self-organize into large energetic microswarms continuously flowing forward with a maximum velocity of 178 μm s−1. Thus, the swarming Fe3O4@PDA-TA NRs can collectively move toward and cover a superficial infection site from a distance, and rapidly eradicate bacteria residing on the surface upon exposure to NIR light due to their efficient photothermal conversion of the Fe3O4 and PDA components. The Fe3O4@PDA-TA NRs achieve a high elimination rate of 99.8% against S. aureus within 10 min under NIR irradiation. Furthermore, they can also penetrate and enter deep-seated infection sites through narrow and tortuous passages, and exert sustained antibacterial action utilizing their inherent chemical activities mainly based on their surface TA-induced easy cell adhesion and subsequent membrane destruction, leading to sustained antibacterial action (chemical bactericidal rate of 89.7% against S. aureus in 24 h). The swarming Fe3O4@PDA-TA NRs show a great potential to execute targeted bacterial elimination at the superficial and deep-seated infection sites simultaneously or sequentially. This work paves a way for the development of future therapeutic microsystems with multifunctional synergies, task flexibility, and high efficiency, potentially applicable to a broader range of diseases.
Materials and Methods
Less
Materials
The superparamagnetic Fe3O4@PVP NPs were fabricated using our previously reported method [51]. Dopamine hydrochloride (DA-HCl) was purchased from Macklin Biochemical Technology Co. Ltd. (Shanghai, China). Tris (hydroxymethyl) aminomethane hydrochloride buffer (tris-HCl; pH 8.5) and TA (95%) were provided by Aladdin Reagent Co. Ltd. (Shanghai, China). Phosphate-buffered saline (PBS; pH 7.4) was acquired from Thermo Fisher Scientific Inc. (USA). Ethanol [analytical reagent (AR)] and sodium chloride (NaCl, AR) were purchased from Sinopharm Chemical Reagent Co. Ltd. (Shanghai, China). Tryptone [biochemical reagent (BR)] and soy peptone (BR) were obtained from Shuangxuan Factory (Beijing, China). Nutrient agar (BR) was achieved from Qingdao Hope Bio-Technology Co. Ltd (Qingdao, China). Syto 9, propidium iodide (PI), and Rhodanmine123 kit were obtained from Beyotime Biotechnology Inc. (Shanghai, China). DI water (18.20 MΩ cm−1) was purified using a Milli-Q system (Millipore, Burlington, MA, USA). All the reagents were used as received without further purification.
Fabrication of Fe3O4@PDA-TA NPs
Typically, Fe3O4@PVP NPs with a diameter of ~150 nm (23.6 mg), DA-HCl (0.33 mg ml−1), and 15 ml of tris-HCl buffer solution (pH 8.5) were mixed in a 3-orifice flask by sonification. The above reaction solution was stirred for 1.5 h while being sonicated, and the dispersion turned from dark brown to gray black. The mixture was centrifuged, and the nanoparticles were collected at the bottom, after which the nanoparticles were rinsed with DI water and ethanol 3 times to remove the unreacted monomers and oligomers. Subsequently, the obtained Fe3O4@PDA NPs (11.8 mg) were redispersed in TA aqueous solution (2.5 mg ml−1) and sonicated for 5 min and left to stay overnight. The dispersion was centrifuged and rinsed with DI water and ethanol 3 times to clear off the unabsorbed TA molecules, and Fe3O4@PDA-TA NPs were stored in DI water for later use.
Characterization
The morphology and structure of the nanoparticles were characterized by a field-emission SEM (Hitachi S-4800, Japan) and a TEM (JEOL, JEM-2100F, Japan). The XPS of the nanoparticles was obtained from the -ray photoelectron spectrometer (Shimadzu, AXIS SUPRA, Japan) at a voltage of 15 kV and a current of 5 mA in the broad spectra and 10 mA in the fine spectra. The FT-IR spectra were measured by a Fourier transform infrared spectrometer (Thermo Fisher Scientific, Nicolet6700, USA). The TG curves were tested by a TG analyzer (NETZSCH, STA449F3, Germany) in the temperature range from 25 to 800°C with a heating rate of 10°C min−1 at air atmosphere. Zeta potentials (ζ) and hydrodynamic sizes were characterized by a Zetasizer Nano ZS90 analyzer (Malvern, UK). The ultraviolet (UV)–visible (vis)–NIR absorption spectra measurement were recorded using a UV-vis-NIR spectrophotometer (PerkinElmer, Lambda 750 S, USA). Reflection spectra of nanoparticle dispersions were measured through a fiber optic spectrometer (Ocean Optics, USB2000+, USA). The magnetic hysteresis loops were tested by a vibrating sample magnetometer (LakeShore 7404s, USA) at 20°C.
Magnetic propulsion of single and swarming Fe3O4@PDA-TA NRs
The magnetic propulsion experiments were conducted in a customized magnetic field system consisting of electric current supplies (ATA-309 Power Amplifiers, China), a signal source (NI USB-6343, USA), and a 3-axis Helmholtz electromagnetic coil. An aqueous suspension of Fe3O4@PDA-TA NPs at a certain concentration (Cp = ~50 μg ml−1 for observation of single NRs and Cp = ~5,000 μg ml−1 for observation of swarming nanorobots) was added dropwise to a glass substrate or a microfluidic channel, and then a permanent magnet (3,000 Gs) was used to collect the dispersed nanoparticles and allow them to settle near the substrate. The Fe3O4@PDA-TA NPs on the substrate were transferred to the coil mounted on an inverted optical microscope (Leica DM3000M, Germany) and then activated and navigated by applying a rotating magnetic field Hr(t) or a precessing magnetic field Hp(t) with different directions, strength H0, and frequency f. All videos were analyzed using Video Spot Tracker V08.01 and ImageJ software.
Photothermal performance testing
Aqueous suspensions (1.0 ml) of Fe3O4@PDA-TA NPs with different concentrations (Cp = 125, 250, 500, and 1,000 μg ml−1) and Fe3O4@PVP and Fe3O4@PDA NPs with Cp of 250 μg ml−1 were added to a standard cuvette and exposed to the NIR laser (808 nm, Leize BOT808-2D200F-S2, China) with different power densities (I) of 0.33, 0.5, 1.0, 1.5, and 2.0 W cm−2 at room temperature (25°C) for 600 s. The temperature of the suspension was recorded at 20-s intervals using a thermography camera (FLIR T420, USA). The UV-vis-NIR absorbance of Fe3O4@PVP, Fe3O4@PDA, and Fe3O4@PDA-TA NP suspensions (Cp = 125 μg ml−1) were tested by a UV-vis-NIR spectrophotometer. Photothermal conversion efficiency (η) of the nanoparticles was calculated in the Supplementary Materials.
Photothermal bacterial elimination
S. aureus bacteria (as a model bacterium) were cultured in the tryptic soy broth (TSB) liquid medium (pH 7.2 to 7.4 with 15 g l−1 tryptone, 5 g l−1 soy peptone, and 5 g l−1 NaCl) in a shaking incubator at 37°C for 12 h to obtain bacterial suspension (~1 × 109 CFU ml−1). Prior to use, all materials underwent sterilization by exposure to UV light. The targeted photothermal elimination of S. aureus bacteria was conducted within a microfluidic chip with 2 open reservoirs interconnected by a narrow canal. A piece of agar gel inoculated with S. aureus colonies was placed at the right reservoir of the microchannel as a simulated superficial infection site, and the swarming Fe3O4@PDA-TA NRs were navigated to cross the canal under Hr(t) (H0 = 20 mT, f = 3 Hz) and then cover the targeted bacteria colonies under Hp(t) (H0 = 20 mT, f = 3 Hz). After coverage, the nanorobots were irradiated by a NIR laser for 10 min to eliminate the bacteria. To evaluate photothermal bacterial elimination at different I, the aqueous dispersions of Fe3O4@PDA-TA NPs were mixed with bacterial suspension (1 × 109 CFU ml−1) in a 24-well plate to form a 1-ml mixture with a Cp of 250 μg ml−1 and followed by irradiation with 808-nm NIR light (0.33, 0.5, and 1.0 W cm−2) for 10 min. The bacteria mixed with DI water and treated without NIR laser, and mixed with DI water and irradiated by NIR laser were set as the control and NIR group, respectively. Bacterial survival rate was then evaluated by the standard agar plate counting method. Briefly, the suspensions were diluted with sterile PBS buffer (pH 7.4, 0.01 M) and spread on a petri dish containing the agar plates to culture for another 12 h at 37°C in an illumination incubator (Hengzi, SPX-150-GBH, China). The number of colonies and bacterial survival rates were calculated. Bacterial survival rate (%) = (number of bacteria colonies in experimental group/number of viable bacteria colonies in control group) × 100%. The tests of each experiment were replicated 3 times. The live/dead staining test was also carried out to visualize living and dead bacteria. Specially, the liquid medium of each group in the 24-well plate was removed, and the bottom bacteria were retained. Dye solution (500 μl) with 5 μM Syto 9 and 5 μM PI was added. After 15 min, the living and dead bacteria in each cell of the 24-well plate were captured by an inverted fluorescence microscope (Leica DM3000B, Germany) (green fluorescence for live bacteria and red fluorescence for dead bacteria).
Chemical bacterial elimination
For targeted chemical bacteria elimination, a piece of agar gel inoculated with S. aureus colonies was placed at the far end of a zigzag microtube to serve as a simulated deep-seated infection site. The swarming Fe3O4@PDA-TA NRs were navigated to cross the microtube under Hr(t) (H0 = 20 mT, f = 3 Hz) and then cover the targeted bacteria colonies under Hp(t) (H0 = 20 mT, f = 3 Hz) for subsequent chemical bacterial elimination. To evaluate the dose-dependent cytotoxicity of the nanoparticles to S. aureus bacteria, 500 μl of bacterial suspension (1 × 109 CFU ml−1) was mixed with aqueous dispersions of Fe3O4@PVP, Fe3O4@PDA, and Fe3O4@PDA-TA NPs in a 24-well plate to prepare 1-ml mixtures with Cp of 31.25, 62.5, 125, and 250 μg ml−1, respectively. The bacterial suspension mixed with 500 μl of DI water was set as the control group. After incubation at 37°C for 24 h, bacterial survival rate was then evaluated by the standard agar plate counting method and the live/dead staining test. In addition, cell membrane permeability of S. aureus bacteria after being cocultured with Fe3O4@PVP, Fe3O4@PDA, and Fe3O4@PDA-TA NP suspensions (Cp =250 μg ml−1) and DI water (as control group) was also tested. Briefly, the culture medium in each cell of 24-well plate was removed. Rhodamine 123 solution (500 μl; 10 μM) was added and dyed in the dark for 30 min. The fluorescence microscopic images were captured by an inverted fluorescence microscope (Leica DM3000B, Germany). The fluorescence intensity was measured by a fluorescence spectrophotometer (SHIMADZU, RF-6000, Japan) at an excitation light wavelength of 510 nm.
Cumulative release of TA
To test the cumulative release of TA molecules, 1.375 ml of the aqueous suspension of freshly prepared Fe3O4@PDA-TA NPs (8 mg ml−1) was shaken at 150 rpm under 37°C in a shaking incubator (Yichun, TS-100C, China). At predetermined time points (1, 2, 3, 5, 7, and 12 h), the suspension was centrifuged to separate the released TA from the nanoparticles. The supernatant was collected, and fresh DI water was added to the remaining pellet to maintain the initial volume. The amount of released TA in the supernatant was quantified by UV-vis-NIR spectroscopy at 280 nm using a Shimadzu UV-2550 spectrophotometer (Japan). The cumulative release percentage of TA was calculated as follows: Cumulative released TA (%) = (amount of released TA/total amount of adsorbed TA) × 100%. The experiments were repeated for 3 times.
Funding
Less
  • National Natural Science Foundation of China (52073222)
  • National Key Research and Development Project(2021YFA1201400)
  • Innovation Team in Key Areas of the Innovation Talent Promotion Plan of MOST of China
References
Less
1.
Murray CJL, Ikuta KS, Sharara F, Swetschinski L,Robles Aguilar G, Gray A, Han C, Bisignano C, Rao P, Wool E, et al. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet. 2022;399(10325):629–655.
2.
Levy SB, Marshall B. Antibacterial resistance worldwide: Causes, challenges and responses. Nat Med. 2004;10(12):S122–S129.
3.
Xie M, Gao M, Yun Y, Malmsten M, Rotello VM, Zboril R, Akhavan O, Kraskouski A, Amalraj J, Cai X, et al. Antibacterial nanomaterials: Mechanisms, impacts on antimicrobial resistance and design principles. Angew Chem Int Ed Engl. 2023;62(17): Article e202217345.
4.
Wang Y, Yang Y, Shi Y, Song H, Yu C. Antibiotic-free antibacterial strategies enabled by nanomaterials: Progress and perspectives. Adv Mater. 2020;32(18):Article1904106.
5.
Song X, Liu P, Liu X, Wang Y, Wei H, Zhang J, Yu L, Yan X, He Z. Dealing with MDR bacteria and biofilm in the post-antibiotic era: Application of antimicrobial peptides-based nano-formulation. Mater Sci Eng C. 2021;128: Article 112318.
6.
Cattoir V, Feldan B. Future antibacterial strategies: From basic concepts to clinical challenges. J Infect Dis. 2019;220(3):350–360.
7.
Jia C, Guo Y, Wu F-G. Chemodynamic therapy via Fenton and Fenton-like nanomaterials: Strategies and recent advances. Small. 2022;18(6):Article 2103868.
8.
Chen Y, Gao Y, Chen Y, Liu L, Mo A, Peng Q. Nanomaterials-based photothermal therapy and its potentials in antibacterial treatment. J Control Release. 2020;328:251–262.
9.
Hu X, Zhang H, Wang Y, Shiu B-C, Lin J-H, Zhang S, Lou C-W, Li T-T. Synergistic antibacterial strategy based on photodynamic therapy: Progress and perspectives. Chem Eng J. 2022;450: Article 138129.
10.
Pang X, Li D, Zhu J, Cheng J, Liu G. Beyond antibiotics: Photo/sonodynamic approaches for bacterial theranostics. Nanomicro Lett. 2020;12(1):Article 144.
11.
Liu Y, Ai K, Lu L. Polydopamine and its derivative materials: Synthesis and promising applications in energy, environmental, and biomedical fields. Chem Rev. 2014;114(9):5057–5115.
12.
Wang Z, Wang W, Wamsley M, Zhang D, Wang H. Colloidal polydopamine beads: A photothermally active support for noble metal nanocatalysts. ACS Appl Mater Interfaces. 2022;14(15):17560–17569.
13.
Qi X, Huang Y, You S, Xiang Y, Cai E, Mao R, Pan W, Tong X, Dong W, Ye F, et al. Engineering robust Ag-decorated polydopamine nano-photothermal platforms to combat bacterial infection and prompt wound healing. Adv Sci. 2022;9(11):Article 2106015.
14.
Andoy NMO, Jeon K, Kreis CT, Sullan RMA. Multifunctional and stimuli-responsive polydopamine nanoparticle-based platform for targeted antimicrobial applications. Adv Funct Mater. 2020;30(40):Article 2004503.
15.
Li Z, Chen Z, Chen H, Chen K, Tao W, Ouyang X-K, Mei L, Zeng X. Polyphenol-based hydrogels: Pyramid evolution from crosslinked structures to biomedical applications and the reverse design. Bioact Mater. 2022;17:49–70.
16.
Guo S, Ren Y, Chang R, He Y, Zhang D, Guan F, Yao M. Injectable self-healing adhesive chitosan hydrogel with antioxidative, antibacterial, and hemostatic activities for rapid hemostasis and skin wound healing. ACS Appl Mater Interfaces. 2022;14(30):34455–34469.
17.
Ninan N, Forget A, Shastri VP, Voelcker NH, Blencowe A. Antibacterial and anti-inflammatory pH-responsive tannic acid-carboxylated agarose composite hydrogels for wound healing. ACS Appl Mater Interfaces. 2016;8(42):28511–28521.
18.
Ahmadian Z, Correia A, Hasany M, Figueiredo P, Dobakhti F, Eskandari MR, Hosseini SH, Abiri R, Khorshid S, Hirvonen J, et al. A hydrogen-bonded extracellular matrix-mimicking bactericidal hydrogel with radical scavenging and hemostatic function for pH-responsive wound healing acceleration. Adv Healthc Mater. 2021;10(3):Article 2001122.
19.
Guo Z, Xie W, Lu J, Guo X, Xu J, Xu W, Chi Y, Takuya N, Wu H, Zhao L. Tannic acid-based metal phenolic networks for bio-applications: A review. J Mater Chem B. 2021;9(20):4098–4110.
20.
Liu T, Zhang M, Liu W, Zeng X, Song X, Yang X, Zhang X, Feng J. Metal ion/tannic acid assembly as a versatile photothermal platform in engineering multimodal nanotheranostics for advanced applications. ACS Nano. 2018;12(4):3917–3927.
21.
Miao Q, Pu K. Organic semiconducting agents for deep-tissue molecular imaging: Second near-infrared fluorescence, self-luminescence, and photoacoustics. Adv Mater. 2018;30(49):Article e1801778.
22.
Nelson BJ, Pané S. Delivering drugs with microrobots. Science. 2023;382(6675):1120–1122.
23.
Chen C, Ding S, Wang J. Materials consideration for the design, fabrication and operation of microscale robots. Nat Rev Mater. 2024;9(3):159–172.
24.
Wang B, Kostarelos K, Nelson BJ, Zhang L. Trends in micro-/nanorobotics: Materials development, actuation, localization, and system integration for biomedical applications. Adv Mater. 2021;33(4):Article e2002047.
25.
Zhang Z, Wang L, Chan TKF, Chen Z, Ip M, Chan PKS, Sung JJY, Zhang L. Micro-/nanorobots in antimicrobial applications: Recent progress, challenges, and opportunities. Adv Healthc Mater. 2022;11(6):Article e2101991.
26.
Yang M, Guo X, Mou F, Guan J. Lighting up micro-/nanorobots with fluorescence. Chem Rev. 2023;123(7):3944–3975.
27.
Yang LD, Yu JF, Yang SH, Wang B, Nelson BJ, Zhang L. A survey on swarm microrobotics. IEEE Trans Robot. 2022;38(3):1531–1551.
28.
Wang Y, Chen H, Xie L, Liu J, Zhang L, Yu J. Swarm autonomy: From agent functionalization to machine intelligence. Adv Mater. 2024; Article 2312956.
29.
Che S, Zhang J, Mou F, Guo X, Kauffman JE, Sen A, Guan J. Light-programmable assemblies of isotropic micromotors. Research. 2022;2022:Article 9816562.
30.
Liang X, Mou F, Huang Z, Zhang J, You M, Xu L, Luo M, Guan J. Hierarchical microswarms with leader–follower-like structures: Electrohydrodynamic self-organization and multimode collective photoresponses. Adv Funct Mater. 2020;30(16):Article 1908602.
31.
Yu J, Wang B, Du X, Wang Q, Zhang L. Ultra-extensible ribbon-like magnetic microswarm. Nat Commun. 2018;9(1):Article 3260.
32.
Xie H, Sun M, Fan X, Lin Z, Chen W, Wang L, Dong L, He Q. Reconfigurable magnetic microrobot swarm: Multimode transformation, locomotion, and manipulation. Sci Robot. 2019;4(28): Article eaav8006.
33.
Zhou H, Mayorga-Martinez CC, Pané S, Zhang L, Pumera M. Magnetically driven micro and nanorobots. Chem Rev. 2021;121(8):4999–5041.
34.
Jin D, Zhang L. Collective behaviors of magnetic active matter: Recent progress toward reconfigurable, adaptive, and multifunctional swarming micro/nanorobots. Acc Chem Res. 2022;55(1):98–109.
35.
Wang Q, Zhang L. External power-driven microrobotic swarm: From fundamental understanding to imaging-guided delivery. ACS Nano. 2021;15(1):149–174.
36.
Gao C, Wang Y, Ye Z, Lin Z, Ma X, He Q. Biomedical micro-/nanomotors: From overcoming biological barriers to in vivo imaging. Adv Mater. 2021;33(6):e2000512.
37.
Wu Z, Chen Y, Mukasa D, Pak OS, Gao W. Medical micro/nanorobots in complex media. Chem Soc Rev. 2020;49(22):8088–8112.
38.
Jin D, Yuan K, Du X, Wang Q, Wang S, Zhang L. Domino reaction encoded heterogeneous colloidal microswarm with on-demand morphological adaptability. Adv Mater. 2021;33(37):Article e2100070.
39.
Li L, Yu Z, Liu J, Yang M, Shi G, Feng Z, Luo W, Ma H, Guan J, Mou F. Swarming responsive photonic nanorobots for motile-targeting microenvironmental mapping and mapping-guided photothermal treatment. Nano-Micro Lett. 2023;15(1):141.
40.
Zhang S, Mou F, Yu Z, Li L, Yang M, Zhang D, Ma H, Luo W, Li T, Guan J. Heterogeneous sensor-carrier microswarms for collaborative precise drug delivery toward unknown targets with localized acidosis. Nano Lett. 2024;24(20):5958–5967.
41.
Hwang G, Paula AJ, Hunter EE, Liu Y, Babeer A, Karabucak B, Stebe K, Kumar V, Steager E, Koo H. Catalytic antimicrobial robots for biofilm eradication. Sci Robot. 2019;4(29): Article eaaw2388.
42.
Dong Y, Wang L, Yuan K, Ji F, Gao J, Zhang Z, Du X, Tian Y, Wang Q, Zhang L. Magnetic microswarm composed of porous nanocatalysts for targeted elimination of biofilm occlusion. ACS Nano. 2021;15(3):5056–5067.
43.
Sun M, Chan KF, Zhang Z, Wang L, Wang Q, Yang S, Chan SM, Chiu PWY, Sung JJY, Zhang L. Magnetic microswarm and fluoroscopy-guided platform for biofilm eradication in biliary stents. Adv Mater. 2022;34(34):Article e2201888.
44.
Bhuyan T, Simon AT, Maity S, Singh AK, Ghosh SS, Bandyopadhyay D. Magnetotactic T-Budbots to kill-n-clean biofilms. ACS Appl Mater Interfaces. 2020;12(39):43352–43364.
45.
Ma X, Wang L, Wang P, Liu Z, Hao J, Wu J, Chu G, Huang M, Mair LO, Huang C, et al. An electromagnetically actuated magneto-nanozyme mediated synergistic therapy for destruction and eradication of biofilm. Chem Eng J. 2022;431: Article 133971.
46.
Li J, Shen H, Zhou H, Shi R, Wu C, Chu PK. Antimicrobial micro/nanorobotic materials design: From passive combat to active therapy. Mater Sci Eng R. 2023;152: Article 100712.
47.
Sun B, Kjelleberg S, Sung JJY, Zhang L. Micro- and nanorobots for biofilm eradication. Nat Rev Bioeng. 2024;2(5):367–369.
48.
Yang M, Zhang Y, Mou F, Cao C, Yu L, Li Z, Guan J. Swarming magnetic nanorobots bio-interfaced by heparinoid-polymer brushes for in vivo safe synergistic thrombolysis. Sci Adv. 2023;9(48): Article eadk7251.
49.
Driscoll M, Delmotte B, Youssef M, Sacanna S, Donev A, Chaikin P. Unstable fronts and motile structures formed by microrollers. Nat Phys. 2017;13(4):375–379.
50.
Erel-Unal I, Sukhishvili SA. Hydrogen-bonded multilayers of a neutral polymer and a polyphenol. Macromolecules. 2008;41(11):3962–3970.
51.
Luo W, Ma H, Mou F, Zhu M, Yan J, Guan J. Steric-repulsion-based magnetically responsive photonic crystals. Adv Mater. 2014;26(7):1058–1064.
52.
Tierno P, Golestanian R, Pagonabarraga I, Sagués F. Controlled swimming in confined fluids of magnetically actuated colloidal rotors. Phys Rev Lett. 2008;101(21): Article 218304.
53.
Chu M, Shao Y, Peng J, Dai X, Li H, Wu Q, Shi D. Near-infrared laser light mediated cancer therapy by photothermal effect of Fe3O4 magnetic nanoparticles. Biomaterials. 2013;34(16):4078–4088.
54.
Kaczmarek B. Tannic acid with antiviral and antibacterial activity as a promising component of biomaterials—A minireview. Materials. 2020;13(14):Article 3224.
55.
Cowan Marjorie M. Plant products as antimicrobial agents. Clin Microbiol Rev. 1999;12(4):564–582.
56.
Fu Y, Yang L, Zhang J, Hu J, Duan G, Liu X, Li Y, Gu Z. Polydopamine antibacterial materials. Mater Horiz. 2021;8(6):1618–1633.
57.
Nor YA, Zhou L, Meka AK, Xu C, Niu Y, Zhang H, Mitter N, Mahony D, Yu C. Engineering iron oxide hollow nanospheres to enhance antimicrobial property: Understanding the cytotoxic origin in organic rich environment. Adv Funct Mater. 2016;26(30):5408–5418.
58.
Liu R, Zheng J, Guo R, Luo J, Yuan Y, Liu X. Synthesis of new biobased antibacterial methacrylates derived from tannic acid and their application in UV-cured coatings. Ind Eng Chem Res. 2014;53(27):10835–10840.
59.
Cookson WOCM, Cox MJ, Moffatt MF. New opportunities for managing acute and chronic lung infections. Nat Rev Microbiol. 2018;16(2):111–120.
60.
Dryden MS. Complicated skin and soft tissue infection. J Antimicrob Chemother. 2010;65(Suppl. 3):iii35–iii44.
61.
Soto F, Wang J, Ahmed R, Demirci U. Medical micro/nanorobots in precision medicine. Adv Sci. 2020;7(21):Article e2002203.
62.
Baburova PI, Kladko DV, Lokteva A, Pozhitkova A, Rumyantceva V, Rumyantceva V, Pankov IV, Taskaev S, Vinogradov VV. Magnetic soft robot for minimally invasive urethral catheter biofilm eradication. ACS Nano. 2023;17(21):20925–20938.
63.
Qiao Y, Liu X, Li B, Han Y, Zheng Y, Yeung KWK, Li C, Cui Z, Liang Y, Li Z, et al. Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing. Nat Commun. 2020;11(1):Article 4446.
64.
Hou S, Mahadevegowda SH, Lu D, Zhang K, Chan-Park MB, Duan H. Metabolic labeling mediated targeting and thermal killing of gram-positive bacteria by self-reporting Janus magnetic nanoparticles. Small. 2021;17(2):Article e2006357.
65.
Mayorga-Martinez CC, Zelenka J, Klima K, Kubanova M, Ruml T, Pumera M. Multimodal-driven magnetic microrobots with enhanced bactericidal activity for biofilm eradication and removal from titanium mesh. Adv Mater. 2023;35(23):Article e2300191.
66.
Dong Y, Wang L, Zhang Z, Ji F, TKF C, Yang H, CPL C, Yang Z, Chen Z, Chang WT, et al. Endoscope-assisted magnetic helical micromachine delivery for biofilm eradication in tympanostomy tube. Sci Adv. 2022;8(40): Article eabq8573.
67.
Nurunnabi M, Khatun Z, Nafiujjaman M, Lee DG, Lee YK, Lee D-g, Lee Y-k. Surface coating of graphene quantum dots using mussel-inspired polydopamine for biomedical optical imaging. ACS Appl Mater Interfaces. 2013;5(16):8246–8253.
68.
Liu P-Y, Miao Z-H, Li K, Yang H, Zhen L, Xu C-Y. Biocompatible Fe3+-TA coordination complex with high photothermal conversion efficiency for ablation of cancer cells. Colloids Surf B Biointerfaces. 2018;167:183–190.
69.
Xu W, Lin Z, Pan S, Chen J, Wang T, Cortez-Jugo C, Caruso F. Direct assembly of metal-phenolic network nanoparticles for biomedical applications. Angew Chem Int Ed Engl. 2023;62(45): Article e202312925.
70.
Xu C, Liu Y, Li J, Ning P, Shi Z, Zhang W, Li Z, Zhou R, Tong Y, Li Y, et al. Photomagnetically powered spiky nanomachines with thermal control of viscosity for enhanced cancer mechanotherapy. Adv Mater. 2023;35(8):Article e2204996.
71.
Mou F, Xie Q, Liu J, Che S, Bahmane L, You M, Guan J. ZnO-based micromotors fueled by CO2: The first example of self-reorientation-induced biomimetic chemotaxis. Natl Sci Rev. 2021;8(11): Article nwab066.
72.
Schmidt CK, Medina-Sánchez M, Edmondson RJ, Schmidt OG. Engineering microrobots for targeted cancer therapies from a medical perspective. Nat Commun. 2020;11(1):Article 5618.
Appendix
Less
Year 2024 volume 7 Issue 7
PDF
192
96
Cite this Article
BibTeX
Article Info
doi: 10.34133/research.0438
  • Receive Date：2024-05-11
  • Online Date：2025-08-07
  • Published：2024-07-31
Article Data
Affiliations
History
  • Received：2024-05-11
  • Accepted：2024-07-07
Funding
National Natural Science Foundation of China (52073222)
National Key Research and Development Project(2021YFA1201400)
Innovation Team in Key Areas of the Innovation Talent Promotion Plan of MOST of China
Affiliations
    1State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, China.
    2 Wuhan Institute of Photochemistry and Technology, Wuhan, China.
    3School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.

Corresponding:

* Address correspondence to: (H.M.); (F.M.); (J.G.)
References
Share
https://castjournals.cast.org.cn/joweb/research/EN/10.34133/research.0438
Share to
QR

Scan QR to access full text

Cite this article
BibTeX
Citations
表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
  • BibTeX
  • EndNote
  • RefWorks
  • TxT
Links
Articles
Latest Articles
Most Read
Collections
Updates
Events
News
Multimedia
About
About Us
Contact
No. 86 Xueyuan South Road, Haidian District, Beijing
100081
010-62199257
qkjq@cast.org.cn

Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House