Latest ArticlesNowadays, there are still many challenges to skin regeneration. As a new type of skin substitute, hydrogel has emerging gradually with its excellent properties. However, it is still a challenge to combine with biological active agents to facilitate skin regeneration. Under the circumstance, we synthesized arginine-based poly(ester amide) (Arg-PEA) and hyaluronic acid (HA-MA), and combined them into new hybrid hydrogels via photo-crosslinking. We found that the internal structure and physicochemical properties of hybrid hydrogels were greatly improved with the increase of content of Arg-PEA. Therefore, we designed hybrid hydrogels with 5 wt% and 10 wt% of Arg-PEA content, respectively. Besides, we selected the corresponding anti-inflammatory (CRP, TNF-α) indicators to detect the anti-inflammatory properties of the hybrid hydrogels at the protein level, and the corresponding antioxidant indicators (SOD, GSH/GSSG, MDA) were selected to investigate the antioxidant properties of hybrid hydrogels at the cellular level in vitro. In addition, we also selected relevant genes to test the effect of hybrid hydrogels on fibrosis and vascularization in the process of skin wound healing in vitro and verified them in vivo with a mouse dorsum wound model. The results confirmed that Arg-PEA/HA-MA (AH) hybrid hydrogel was a prospective scaffold material for skin regeneration.
The rapid detection of microparticles exhibits a broad range of applications in the field of science and technology. The proposed method differentiates and identifies the 2 µm and 5 µm sized particles using a laser light scattering. The detection method is based on measuring forward light scattering from the particles and then classifying the acquired data using support vector machines. The device is composed of a microfluidic chip linked with photosensors and a laser device using optical fiber. Connecting the photosensors and laser device using optical fibers makes the device more diminutive in size and portable. The prepared sample containing microspheres was passed through the channel, and the surrounding photosensors measured the scattered light. The time-domain features were evaluated from the acquired scattered light, and then the SVM classifier was trained to distinguish the particle's data. The real-time detection of the particles was performed with an overall classification accuracy of 96.06%. The optimum conditions were evaluated to detect the particles with a minimum concentration of 0.2 µg/mL. The developed system is anticipated to be helpful in developing rapid testing devices for detecting pathogens ranging between 2 µm to 10 µm.
Permeation enhancers (PEs), such as N-[8-(2-hydroxybenzoyl)amino]-caprylate (SNAC), have been reported to improve the oral absorption of various macromolecules. However, the bioavailabilities of these formulations are quite low and variable due to the influences of enzymes, pH and other gastrointestinal barriers. In this study, we revealed that SNAC could interact with insulin to form tight complexes in a specific concentration (insulin ≥ 40 µg/mL)-, ratio (SNAC/insulin ≥ 20:1)- and pH (≥ 6.8)-dependent manner, thus contributing to a significantly high efficacy of oral insulin delivery. Specifically, absorption mechanism studies revealed that the SNAC/insulin complexes were internalized into the cells by passive diffusion and remained intact when transported in the cytosol. Furthermore, the complexes accelerated the exocytosis of insulin to the basolateral side, thereby enhancing its intestinal mucosal permeability. Eudragit® S100-entrapped SNAC/insulin microspheres were then prepared and exhibited an apparent permeability coefficient (Papp) that was 6.6-fold higher than that of the insulin solution. In diabetic rats, hypoglycemic activity was sustained for more than 10 h after the microspheres were loaded into enteric-coated capsules. Further pharmacokinetic studies revealed an approximately 6.3% oral bioavailability in both the fasted and fed states, indicating a negligible food effect. Collectively, this study provides insight into the interaction between PEs and payloads and presents an SNAC-based oral insulin delivery system that has high oral bioavailability and patient-friendly medication guidance.
Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinated nanomedicines for mild hyperthermia-assisted anti-cancer ferroustherapy. In brief, Fe-GA@BSA nanoparticles was synthesized by self-assembly and sorafenib (SRF) was loaded into Fe-GA@BSA to establish Fe-GA@BSA-SRF nanomedicines. The result nanomedicines can induce ferroptosis in cancer cells by accelerating Fenton reaction. And the photothermal effect of Fe-GA@BSA-SRF was used for mild hyperthermia-assisted ferroustherapy. The nanomedicines performs good anti-cancer therapeutic efficacy by inducing the production of ROS and inhibiting glutathione peroxidase 4 (GPX4) expression in vitro and in vivo. Besides, the broad absorption of Fe-GA@BSA-SRF in near infrared region endows it with photoacoustic imaging ability. This study provides ideas about rational design on iron-based nanoparticles for anti-cancer ferroustherapy.
Neuroinflammation plays a significant role in inducing depression-like behavior. Tetrahedral DNA nanostructures (TDNs) are molecules that exhibit anti-inflammatory properties and can effectively penetrate the blood-brain barrier. Thus, researchers have hypothesized that TDNs regulate the secretion of proinflammatory cytokines and consequently alleviate depression-like behavior. To test this hypothesis, we investigated the effect of TDNs on the depression-like behavior of C57 mice induced by lipopolysaccharide (LPS). We performed open-field, tail suspension, and sucrose preference tests on LPS- and LPS/TDN-treated mice. The results indicated that the injection of TDNs into LPS-treated mice resulted in increased velocity, center zone duration, frequency to the center zone, and sucrose preference, and decreased immobility time. Immunofluorescence results indicated that peripheral administration of LPS in the mice activated inflammation, which culminated in distinct depression-like behavior. However, TDNs effectively alleviated the inflammation and depression-like behavior through the reduction of the expression levels of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α in the brain. Additionally, TDNs normalized the expression level of microglia cell activation markers, such as ionized calcium binding adaptor molecule 1, in the hippocampus of mice. These results indicated that TDNs attenuated the LPS-induced secretion of inflammatory factors and consequently alleviated depression-like behavior.
Metal-based compounds with excellent photo-physical properties show good photochemotherapeutic performance. But, low in-depth tissue penetration of light limits their effectivity for deeply buried tumors. Encouraged by the sonosensitizing ability of the traditional organic photosensitizers, here, we developed AuNPs@Ir1 as a sonosensitizer by hybridizing an organometallic Ir(Ⅲ) complex (Ir1) with ultrasmall gold nanoparticles (AuNPs) for efficient tumor sonodynamic therapy (SDT) for the first time. AuNPs@Ir1 rapidly entered the cancer cells, produced 1O2, and catalytically oxidized NADH to NAD+ under ultrasound (US) irradiation, thus resulted in cancer cells oncosis. Because of efficient passive retention in tumors post intravenous injection, AuNPs@Ir1 further efficiently inhibited the growth of tumors in-vivo under US stimulation without long-term toxicity to other organs. Overall, this work presents the excellent US triggered in-vitro and in-vivo anticancer profile of the novel AuNPs@Ir1. It is expected to increase the scope of SDT for metal-based anticancer drugs.
In this work, a simple gold nanoparticles (AuNPs) based colorimetric biosensor was developed for chlorpyrifos (Chl) detection using an aptamer as the capture probe. The Chl-aptamer with low dissociation constant (Kd) of 58.59 ± 6.08 nmol/L was selected by ssDNA library immobilized systematic evolution of ligands by enrichment (SELEX). In the absence of Chl, the Chl-aptamer acted as the stabilizer for AuNPs in salt solution. In the presence of Chl, the highly specific Chl-aptamer bound with Chl targets immediately, thus a self-aggregation of AuNPs induced by salt was displayed. The fabricated colorimetric aptasensor exhibited an excellent sensitivity for Chl detection with the LOD as low as 14.46 nmol/L. In addition, the aptasensor was applied to test Chl in tap water, cucumber and cabbage samples, the excellent recoveries with acceptable RSD values below 5% demonstrated that the method can be considered as a promising tool for simple, rapid Chl detection.
The intrinsic hypoxic tumor microenvironment and limited accumulation of photosensitizers (PSs) result in unsatisfied efficiency of photodynamic therapy (PDT). To enhance the PDT efficiency against solid tumors, a functional oxygen self-supplying and PS-delivering nanosystem is fabricated via the combination of catalase (CAT), chlorin e6 (Ce6) and metal-phenolic network (MPN) capsule. It is demonstrated that the CAT encapsulated in the capsules (named CCM capsules) could catalyze the degradation of hydrogen peroxide (H2O2) to produce molecular oxygen (O2), which could be converted into cytotoxicity reactive oxygen species (ROS) by surface-loaded Ce6 under 660 nm laser irradiation, leading to synergistic anticancer effects in vitro and in vivo. Therefore, the application of CCM capsule could be a promising strategy to improve PDT effectiveness.
Light-responsive carriers have been used for the controlled release of antitumor drugs in recent years. However, most light-responsive vectors require high-energy ultraviolet or visible light to achieve local drug release, and ultraviolet light would cause cellular damage. Near-infrared light has a deeper tissue-penetration depths and minimal harm to tissues, but it is difficult to cleave the chemical bond directly. The aim of this study is to develop a novel near-infrared light-responsive carrier for local release of antitumor drugs. Unsaturated phospholipids can be oxidized by singlet oxygen to achieve liposomal drug release, and singlet oxygen can be produced by photosensitizer under light irradiation. A new near-infrared light-responsive nanoliposome was designed that imparts light-triggered local drug release. Nanoliposomes, which were composed of matrix phospholipids and unsaturated phospholipids, were prepared by ammonium sulfate gradient method, and loaded with antitumor drug doxorubicin (DOX) and photosensitizer 1, 4, 8, 11, 15, 18, 22, 25-octabutoxypalladium phthalocyanine. Under near-infrared light, photosensitizers could produce singlet oxygen and damage tumor cells by photodynamic therapy. Simultaneously, the unsaturated phospholipids were oxidized by singlet oxygen and result in DOX release, causing sustained cell damage by chemotherapy. Near-infrared light-responsive nanoliposomes exhibit enhanced anticancer activity owing to combined treatment of photodynamic therapy and chemotherapy. A new platform is thus offered for designing effective intracellular drug-release systems, holding great promise for future cancer therapy.
Photodynamic therapy (PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species (ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway (UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib (BTZ, a proteasome inhibitor) and pyropheophorbide a (PPa) for proteasome inhibition-mediated PDT sensitization. The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment, good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.
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