ArchiveBenefiting from treating diseases at the genetic level, gene therapy has been considered a new revolution in the biomedical field. However, the extracellular and intracellular barriers during gene transport such as enzymatic degradation and endo-/lysosomal sequestration significantly compromise the therapeutic efficacy. Though photochemical internalization (PCI) has emerged as a promising approach for causing endo-/lysosomal leakage with translocation of the internalized molecules into the cytosol, its effect is still unsatisfactory due to the insufficient light penetration depth. Here, we develop tumor microenvironment-specific enhanced gene delivery by means of ROS generated from the in situ cascaded catalytic reactions in tumors involving GOx-mediated redox reaction and Mn2+-mediated Fenton-like reaction. The efficient enzymatic protection and successful endo-/lysosomal escape of cargo gene complexes have been demonstrated. Moreover, anti-Twist siRNA-loaded G@MMSNs-P exhibit tumor-specific biodegradation, excellent T1-weighted MR imaging, and significant inhibitory effects against breast cancer growth and pulmonary metastasis.
The therapeutic outcomes of noninvasive sonodynamic therapy (SDT) are always compromised by tumor hypoxia, as well as inherent protective mechanisms of tumor. Herein, we report a simple cascade enzymatic approach of the concurrent glucose depletion and intratumoral oxygenation for starvation-sensitized and oxygenation-amplified sonodynamic therapy using a dual enzyme and sonosensitizer-loaded nanomedicine designated as GOD/CAT@ZPF-Lips. In particular, glucose oxidase- (GOD-) catalyzed glycolysis would cut off glucose supply within the tumor, resulting in the production of tumor hydrogen peroxide (H2O2) while causing tumor cells starvation. The generated H2O2 could subsequently be decomposed by catalase (CAT) to generate oxygen, which acts as reactants for the abundant singlet oxygen (1O2) production by loaded sonosensitizer hematoporphyrin monomethyl ether (HMME) upon the US irradiation, performing largely elevated therapeutic outcomes of SDT. In the meantime, the severe energy deprivation enabled by GOD-catalyzed glucose depletion would prevent tumor cells from executing protective mechanisms to defend themselves and make the tumor cells sensitized and succumbed to the cytotoxicity of 1O2. Eventually, GOD/CAT@ZPF-Lips demonstrate the excellent tumoral therapeutic effect of SDT in vivo without significant side effect through the cascade enzymatic starvation and oxygenation, and encouragingly, the tumor xenografts have been found completely eradicated in around 4 days by the intravenous injection of the nanomedicine without reoccurrence for as long as 20 days.
Sensors capable of monitoring dynamic mechanics of tendons throughout a body in real time could bring systematic information about a human body’s physical condition, which is beneficial for avoiding muscle injury, checking hereditary muscle atrophy, and so on. However, the development of such sensors has been hindered by the requirement of superior portability, high resolution, and superb conformability. Here, we present a wearable and stretchable bioelectronic patch for detecting tendon activities. It is made up of a piezoelectric material, systematically optimized from architectures and mechanics, and exhibits a high resolution of with a linearity parameter of . Additionally, a tendon real-time monitoring and healthcare system is established by integrating the patch with a micro controller unit (MCU), which is able to process collected data and deliver feedback for exercise evaluation. Specifically, through the patch on the ankle, we measured the maximum force on the Achilles tendon during jumping which is about 16312 N, which is much higher than that during normal walking (3208 N) and running (5909 N). This work not only provides a strategy for facile monitoring of the variation of the tendon throughout the body but also throws light on the profound comprehension of human activities.
Aggregation-induced emission nanoparticles (AIE NPs) are widely used in the biomedical field. However, understanding the biological process of AIE NPs via fluorescence imaging is challenging because of the strong background and poor penetration depth. Herein, we present a novel dual-modality imaging strategy that combines fluorescence imaging and label-free laser desorption/ionization mass spectrometry imaging (LDI MSI) to map and quantify the biodistribution of AIE NPs (TPAFN-F127 NPs) by monitoring the intrinsic photoluminescence and mass spectrometry signal of the AIE molecule. We discovered that TPAFN-F127 NPs were predominantly distributed in the liver and spleen, and most gradually excreted from the body after 5 days. The accumulation and retention of TPAFN-F127 NPs in tumor sites were also confirmed in a tumor-bearing mouse model. As a proof of concept, the suborgan distribution of TPAFN-F127 NPs in the spleen was visualized by LDI MSI, and the results revealed that TPAFN-F127 NPs were mainly distributed in the red pulp of the spleen with extremely high concentrations within the marginal zone. The in vivo toxicity test demonstrated that TPAFN-F127 NPs are nontoxic for a long-term exposure. This dual-modality imaging strategy provides some insights into the fine distribution of AIE NPs and might also be extended to other polymeric NPs to evaluate their distribution and drug release behaviors in vivo.
Shape-morphing hydrogels can be widely used to develop artificial muscles, reconfigurable biodevices, and soft robotics. However, conventional approaches for developing shape-morphing hydrogels highly rely on composite materials or complex manufacturing techniques, which limit their practical applications. Herein, we develop an unprecedented strategy to edit the shape morphing of monocomponent natural polysaccharide hydrogel films via integrating gradient cross-linking density and geometry effect. Owing to the synergistic effect, the shape morphing of chitosan (CS) hydrogel films with gradient cross-linking density can be facilely edited by changing their geometries (length-to-width ratios or thicknesses). Therefore, helix, short-side rolling, and long-side rolling can be easily customized. Furthermore, various complex artificial 3D deformations such as artificial claw, horn, and flower can also be obtained by combining various flat CS hydrogel films with different geometries into one system, which can further demonstrate various shape transformations as triggered by pH. This work offers a simple strategy to construct a monocomponent hydrogel with geometry-directing programmable deformations, which provides universal insights into the design of shape-morphing polymers and will promote their applications in biodevices and soft robotics.
Metal-enhanced photocatalysis has recently received increasing interest, mainly due to the ability of metal to directly or indirectly degrade pollutants. In this review, we briefly review the recent breakthroughs in metal-enhanced photocatalysis. We discussed the recent progress of surface plasmon resonance (SPR) effect and small size effect of metal nanoparticles on photocatalysis; in particular, we focus on elucidating the mechanism of energy transfer and hot electron injection/transfer effect of metal nanoparticles and clusters while as photocatalysts or as cophotocatalysts. Finally, we discuss the potential applications of metal-enhanced photocatalysis, and we also offer some perspectives for further investigations.
Organic-inorganic hybrid perovskites (OIHPs) have been intensively studied due to their fascinating optoelectronic performance. Electron microscopy and related characterization techniques are powerful to figure out their structure-property relationships at the nanoscale. However, electron beam irradiation usually causes damage to these beam-sensitive materials and thus deteriorates the associated devices. Taking a widely used CH3NH3PbI3 film as an example, here, we carry out a comprehensive study on how electron beam irradiation affects its properties. Interestingly, our results reveal that photoluminescence (PL) intensity of the film can be significantly improved along with blue-shift of emission peak at a specific electron beam dose interval. This improvement stems from the reduction of trap density at the CH3NH3PbI3 surface. The knock-on effect helps expose a fresh surface assisted by the surface defect-induced lowering of displacement threshold energy. Meanwhile, the radiolysis process consistently degrades the crystal structure and weaken the PL emission with the increase of electron beam dose. Consequently, the final PL emission comes from a balance between knock-on and radiolysis effects. Taking advantage of the defect regulation, we successfully demonstrate a patterned CH3NH3PbI3 film with controllable PL emission and a photodetector with enhanced photocurrent. This work will trigger the application of electron beam irradiation as a powerful tool for perovskite materials processing in micro-LEDs and other optoelectronic applications.
Stem cell therapy holds high promises in regenerative medicine. The major challenge of clinical translation is to precisely and quantitatively evaluate the in vivo cell distribution, migration, and engraftment, which cannot be easily achieved by current techniques. To address this issue, for the first time, we have developed a molecular cell tracker with a strong fluorescence signal in the second near-infrared (NIR-II) window (1,000-1,700 nm) for real-time monitoring of in vivo cell behaviors in both healthy and diseased animal models. The NIR-II tracker (CelTrac1000) has shown complete cell labeling with low cytotoxicity and profound long-term tracking ability for 30 days in high spatiotemporal resolution for semiquantification of the biodistribution of transplanted stem cells. Taking advantage of the unique merits of CelTrac1000, the responses of transplanted stem cells to different diseased environments have been discriminated and unveiled. Furthermore, we also demonstrate CelTrac1000 as a universal and effective technique for ultrafast real-time tracking of the cellular migration and distribution in a 100 μm single-cell cluster spatial resolution, along with the lung contraction and heart beating. As such, this NIR-II tracker will shift the optical cell tracking into a single-cell cluster and millisecond temporal resolution for better evaluating and understanding stem cell therapy, affording optimal doses and efficacy.
Australia is a warm country with well-developed agriculture and a highly urbanized population. How these specific features impact the nitrogen cycle, emissions, and consequently affect environmental and human health is not well understood. Here, we find that the ratio of reactive nitrogen () losses to air over losses to water in Australia is 1.6 as compared to values less than 1.1 in the USA, the European Union, and China. Australian emissions to air increased by more than 70% between 1961 and 2013, from 1.2 Tg N yr-1 to 2.1 Tg N yr-1. Previous emissions were substantially underestimated mainly due to neglecting the warming climate. The estimated health cost from atmospheric emissions in Australia is 4.6 billion US dollars per year. Emissions of to the environment are closely correlated with economic growth, and reduction of losses to air is a priority for sustainable development in Australia.
Large-size organic halide passivation has been considered an efficient approach to enhance the perovskite solar cell (PSC) efficiency and stability. Herein, a facile posttreatment strategy was demonstrated, wherein trifluoromethyl-phenethylamine hydrobromide (CF3-PEABr) is firstly used to passivate the perovskite film surface. The CF3-PEABr surface posttreatment could coordinate with halide dangling bonds that exist at the perovskite crystal surface. Moreover, the surface treatment with CF3-PEABr could efficiently passivate the defects in the perovskite film and suppress the nonradiative carrier recombination. As a result, a high efficiency of 21.3% is obtained, and an increment of 80 mV in (a large of 1.15 V, with a 0.42 V voltage deficit) occurs, compared to the control device. To relieve the hydrophobic nature properties of the -CF3 functional group and the dewetting problem of PCBM layer deposition, a surfactant Triton X-100 is used to modify the PCBM layer. Furthermore, the devices with CF3-PEABr posttreatment exhibit better operational, thermal (85°C), and long storage stabilities without any encapsulation.
Wound healing is a complex physiological process that involves coordinated phases such as inflammation and neovascularization. Attempts to promote the healing process tend to construct an effective delivery system based on different drugs and materials. In this paper, we propose novel MXene-integrated microneedle patches with adenosine encapsulation for wound healing. Owing to the dynamic covalent bonding capacity of boronate molecules with adenosine, 3-(acrylamido)phenylboronic acid- (PBA-) integrated polyethylene glycol diacrylate (PEGDA) hydrogel is utilized as the host material of microneedle patches. Benefitting from photothermal conversion capacity of MXene, the release of loaded adenosine could be accelerated under NIR irradiation for maintaining the activation signal around injury site. In vitro cell experiments proved the effect of MXene-integrated microneedle patches with adenosine encapsulation in enhancing angiogenesis. When applied for treating animal models, it is demonstrated that the microneedle patches efficiently promote angiogenesis, which is conductive to wound healing. These features make the proposed microneedle patch potential for finding applications in wound healing and other biomedical fields.
Real-time wireless respiratory monitoring and biomarker analysis provide an attractive vision for noninvasive telemedicine such as the timely prevention of respiratory arrest or for early diagnoses of chronic diseases. Lightweight, wearable respiratory sensors are in high demand as they meet the requirement of portability in digital healthcare management. Meanwhile, high-performance sensing material plays a crucial role for the precise sensing of specific markers in exhaled air, which represents a complex and rather humid environment. Here, we present a liquid metal-based flexible electrode coupled with SnS2 nanomaterials as a wearable gas-sensing device, with added Bluetooth capabilities for remote respiratory monitoring and diagnoses. The flexible epidermal device exhibits superior skin compatibility and high responsiveness (1092%/ppm), ultralow detection limits (1.32 ppb), and a good selectivity of NO gas at ppb-level concentrations. Taking advantage of the fast recovery kinetics of SnS2 responding to H2O molecules, it is possible to accurately distinguish between different respiratory patterns based on the amount of water vapor in the exhaled air. Furthermore, based on the different redox types of H2O and NO molecules, the electric signal is reversed once the exhaled NO concentration exceeds a certain threshold that may indicate the onset of conditions like asthma, thus providing an early warning system for potential lung diseases. Finally, by integrating the wearable device into a wireless cloud-based multichannel interface, we provide a proof-of-concept that our device could be used for the simultaneous remote monitoring of several patients with respiratory diseases, a crucial field in future digital healthcare management.
Metal-organic frameworks (MOFs) have attracted significant attention in the past two decades due to their diverse physical properties and associated functionalities. Although numerous advances have been made, the acoustic properties of MOFs have attracted very little attention. Here, we systematically investigate the acoustic velocities and impedances of 19 prototypical MOFs via first-principle calculations. Our results demonstrate that these MOFs exhibit a wider range of acoustic velocities, higher anisotropy, and lower acoustic impedances than their inorganic counterparts, which are ascribed to their structural diversity and anisotropy, as well as low densities. In addition, the piezoelectric properties, which are intimately related to the acoustic properties, were calculated for 3 MOFs via density functional perturbation theory, which reveals that MOFs can exhibit significant piezoelectricity due to the ionic contribution. Our work provides a comprehensive study of the fundamental acoustic properties of MOFs, which could stimulate further interest in this new exciting field.
Reliable, wide range, and highly sensitive joint movement monitoring is essential for training activities, human behavior analysis, and human-machine interfaces. Yet, most current motion sensors work on the nano/microcracks induced by the tensile deformation on the convex surface of joints during joint movements, which cannot satisfy requirements of ultrawide detectable angle range, high angle sensitivity, conformability, and consistence under cyclic movements. In nature, scorpions sense small vibrations by allowing for compression strain conversion from external mechanical vibrations through crack-shaped slit sensilla. Here, we demonstrated that ultraconformal sensors based on controlled slit structures, inspired by the geometry of a scorpion’s slit sensilla, exhibit high sensitivity (0.45%deg-1), ultralow angle detection threshold (~15°), fast response/relaxation times (115/72 ms), wide range (15° ~120°), and durability (over 1000 cycles). Also, a user-friendly, hybrid sign language system has been developed to realize Chinese and American sign language recognition and feedback through video and speech broadcasts, making these conformal motion sensors promising candidates for joint movement monitoring in wearable electronics and robotics technology.
Aggregation-induced emission (AIE) has been much employed for visualizing material aggregation and self-assembly. However, water is generally required for the preparation of the AIE aggregates, the operation of which limits numerous material processing behaviors. Employing hexathiobenzene-based small molecules, monopolymers, and block copolymers as different material prototypes, we herein achieve AIE in pure organic phases by applying a nonequilibrium strategy, photoexcitation-controlled aggregation. This strategy enabled a dynamic change of molecular conformation rather than chemical structure upon irradiation, leading to a continuous aggregation-dependent luminescent enhancement (up to ~200-fold increase of the luminescent quantum yield) in organic solvents. Accompanied by the materialization of the nonequilibrium strategy, photoconvertible self-assemblies with a steady-state characteristic can be achieved upon organic solvent processing. The visual monitoring with the luminescence change covered the whole solution-to-film transition, as well as the in situ photoprocessing of the solid-state materials.