Biomimetic Metal-Chalcogenide Agents Enable Synergistic Cancer Therapy via Microwave Thermal-Dynamic Therapy and Immune Cell Activation.

Microwave thermal dynamic therapy (MTDT), which combines thermal effects and reactive oxygen species (ROS) by microwave activation, seems to be a promising anticancer therapeutic method. A multifunctional agent for achieving synergistic localized cancer treatment is the key to exploit the strategy to inhibit tumor cell recurrence and metastasis. In the study, a ZIF-67 based theranostic agent loaded with metal-chalcogenide open framework 3 (MCOF3) and heat shock protein 70 (HSP70) as the inner component was studied, coupled with targeting cancer cell membrane (TCM) as the biomimetic outer shell. We found that metal ions in MCOF3 enabled the composite agents to show peroxide-like activity to produce •OH and destroy cancer cells. And then, the microwave (MW) thermal sensitizer of ZIF-67 was used to specifically convert the MW energy into thermal energy and selectively heat the tumor via the cell's targeting. Additionally, the effect of continuous MW thermal therapy has been shown to promote the expression of HSP70, and further activate the effector of CD4 T cell and CD8α T cell. As such, the agents effectively inhibit the tumor cell growth under MW irradiation in vitro and in vivo due to the synergistic effects of MTDT and immune cell activation. The study provides an emerging strategy to ablation cancer effectively.

Autocatalytically hydroxyl-producing composite wound dressing for bacteria-infected wound healing.

The creation of wound dressings with low drug resistance and broad-spectrum antibacterial capability is a key topic of scientific interest. To achieve this, a bactericidal wound dressing with the capacity to autocatalytically produce hydroxyl radicals (OH) was developed. The wound dressing was an electrospun PCL/gelatin/glucose composite fiber mesh (PGD) with functional iron-containing metal-organic framework (Fe-MOF) nanozymes. These functional nanozymes (G@Fe) were formed by coupling glucose oxidase (GOx) and Fe-MOF through amide bonds. These nanozymes enabled the conversion of glucose released from the PGD composite mesh into hydroxyl radicals via an autocatalytic cascade reaction to destroy bacteria. The antibacterial efficiency of wound dressings and their stimulation of tissue regeneration were assessed using a MRSA-infected skin wound infection model on the back of SD mice. The G@Fe/PGD wound dressing exhibited improved wound healing capacity and had comparable biosafety to commercial silver-containing dressings, suggesting a potential replacement in the future.

High-Efficiency Near-Infrared Light Responsive Antibacterial System for Synergistic Ablation of Bacteria and Biofilm.

Bacterial infection is seriously threatening human health, and the design of high-efficiency and good biocompatibility antibacterial agents is an urgent problem to be solved. However, with the emergence of drug-resistant bacteria, the existing antibacterial agents have low killing efficiency, and the formation of biofilms has further weakened the therapeutic effect. Herein, we constructed an efficient antibacterial system mediated by near-infrared light for synergistic antibacterial and biofilm dissipation. Specifically, the ZnO/Ti3C2Tx with heterojunction was synthesized by hydrothermal growth of ZnO on the surface of lamellar Ti3C2Tx-MXene. The prepared ZnO/Ti3C2Tx had better photothermal ability than ZnO and Ti3C2Tx, respectively. The local thermal effect can not only destroy the integrity of the bacterial membrane but also promote the release of Zn2+ ions and further improve the antibacterial performance. ZnO/Ti3C2Tx achieved a 100% sterilization rate (better than either ZnO or Ti3C2Tx) at 150 µg mL-1. The biofilm dissipation experiment further proved its excellent biofilm ablation effect. More importantly, the results of in vitro cell culture and animal experiments have demonstrated its good biological safety. In summary, this new type of nanomaterial shows strong local chemical photothermal sterilization ability and has great potential to replace traditional antibacterial agents.

PLGA-coated methylene blue nanoparticles for photoacoustic imaging and photodynamic/photothermal cascaded precisely synergistic therapy of tumor.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are synergetic treatment strategies in antitumor treatment to achieve the best anticancer efficacy. Although traditional photosensitizer materials such as methylene blue (MB) have been widely studied for PDT, the photothermal effect is rarely reported. Herein, mono-component nanoparticles lactic-co-glycolic acid-coated methylene blue (MBNPs) based on methylene blue (MB) and lactic-co-glycolic acid (PLGA) were prepared by a facile solution-based emulsification method at room temperature. The resulting nanoparticles possess high photothermal conversion efficiency and excellent photodynamic effect. For the first time, the in vitro and in vivo tests indicated an enhanced antitumor efficacy for MBNPs with combined PDT and PTT. This study provides an efficient approach to fabricate nano-MB and also demonstrates the great potential of lactic-co-glycolic acid-coated MB for biomedical applications. Most importantly, the strong tumor growth inhibition by synergistic PTT and PDT demonstrates an excellent cascaded synergistic effect of MBNPs for the tumor therapy.

In vivo and in vitro evaluation of chitosan-modified bioactive glass paste for wound healing.

In this work, the role of chitosan (CS) in improving the properties of bioactive glass (BG) paste for wound healing was studied. Based on in vitro evaluation, it was found that the addition of CS neutralizes the pH value from 11.0 to 7.5, which did not lead to decreasing the bioactivity of BG paste in vitro. The rheological properties showed that the composite paste had higher bio-adhesion and better affinity with the skin surface than either CS or the BG paste. The antibacterial property evaluation showed that the composite paste had stronger antibacterial activity than either CS or BG paste and promoted the proliferation of HUVECs (human umbilical vein endothelial cells) and HaCat (human immortalized keratinocyte cells). Comparatively, the effect of promoting the proliferation of HUVECs is more significant than that of HaCat. The burn-wound model of rat was developed for evaluating in vivo activity, and the addition of CS effectively promoted wound healing without obvious inflammation according to the IL-1ß and IL-6 staining. This novel paste is expected to provide a promising alternative for wound healing.

Poly Lactic-co-Glycolic Acid-Coated Toluidine Blue Nanoparticles for the Antibacterial Therapy of Wounds.

Bacterial infections in wounded skin are associated with high mortality. The emergence of drug-resistant bacteria in wounded skin has been a challenge. Toluidine blue (TB) is a safe and inexpensive photosensitizer that can be activated and used in near-infrared photodynamic therapy to effectively kill methicillin-resistant Staphylococcus aureus (MRSA). However, its aggregation-induced quenching effect largely affects its clinical applications. In this study, TB nanoparticles (NPs) were synthesized using an ultrasound-assisted coating method. Their physicochemical and biological properties were studied and evaluated by scanning electron microscopy and Fourier-transform infrared spectroscopy. The TBNPs had a broad-spectrum antibacterial activity against Gram-positive bacteria (MRSA) and Gram-negative bacteria (E. coli). In addition, MTT, hemolysis, and acute toxicity tests confirmed that TBNPs had good biocompatibility. The TBNPs exhibited a high photodynamic performance under laser irradiation and efficiently killed E. coli and MRSA through generated reactive oxygen species, which destroyed the cell wall structure. The potential application of TBNPs in vivo was studied using an MRSA-infected wound model. The TBNPs could promote wound healing within 7 days, mainly by reducing the inflammation and promoting collagen deposition and granulation tissue formation. In conclusion, the TBNPs offer a promising strategy for clinical applications against multiple-drug resistance.

Cu-Doped-ZnO Nanocrystals Induce Hepatocyte Autophagy by Oxidative Stress Pathway.

As a novel nanomaterial for cancer therapy and antibacterial agent, Cu-doped-ZnO nanocrystals (CZON) has aroused concern recently, but the toxicity of CZON has received little attention. Results of hematology analysis and blood biochemical assay showed that a 50 mg/kg dosage induced the increase in white blood cells count and that the concentration of alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), and Malonaldehyde (MDA) in the serum, liver, and lungs of the CZON group varied significantly from the control mice. Histopathological examinations results showed inflammation and congestion in the liver and lung after a single injection of CZON at 50 mg/kg. A transmission electron microscope (TEM) result manifested the autolysosome of hepatocyte of mice which received CZON at 50 mg/kg. The significant increase in LC3-II and decrease in p62 of hepatocyte in vivo could be seen in Western blot. These results indicated that CZON had the ability to induce autophagy of hepatocyte. The further researches of mechanism of autophagy revealed that CZON could produce hydroxyl radicals measured by erythrocyte sedimentation rate (ESR). The result of bio-distribution of CZON in vivo, investigated by ICP-OES, indicated that CZON mainly accumulated in the liver and two spleen organs. These results suggested that CZON can induce dose-dependent toxicity and autophagy by inducing oxidative stress in major organs. In summary, we investigated the acute toxicity and biological distribution after the intravenous administration of CZON. The results of body weight, histomorphology, hematology, and blood biochemical tests showed that CZON had a dose-dependent effect on the health of mice after a single injection. These results indicated that CZON could induce oxidative damage of the liver and lung by producing hydroxyl radicals at the higher dose.

Lactic-co-glycolic acid-coated methylene blue nanoparticles with enhanced antibacterial activity for efficient wound healing.

Effective wound healing has been demonstrated using lactic-co-glycolic acid (PLGA)-coated methylene blue nanoparticles (MPNPs) as a novel susceptible agent for photodynamic antibacterial therapy. Compared with methylene blue (MB) solution, MPNPs have a significantly improved antibacterial effect in vitro and in vivo. The enhanced antibacterial effect is achieved through increased singlet oxygen generation in MPNPs compared to that of MB solution, as a result of the decreased aggregation-induced quenching (ACQ) effect of the MPNPs. The mouse skin infection model experiment proved that MPNP has good antibacterial effects and promotes wound healing.

Cu2ZnSnS4 nanocrystals for microwave thermal and microwave dynamic combination tumor therapy.

Cu2ZnSnS4 nanocrystals (CZTS NCs) have been demonstrated to be effective in tumor therapy as a novel susceptible agent for microwave thermal and microwave dynamic therapy. CZTS NCs intensify the heating effect of microwaves with a significant temperature increase of about 15 °C compared to the control group and showed remarkable anti-tumor performance after 5 min of microwave irradiation. For the first time, we report the microwave absorption performance and singlet oxygen production of CZTS NCs used in microwave therapy, which reveals new opportunities for novel combined mechanisms of microwave thermal and microwave dynamic tumor therapies.

Detection of dysregulated competing endogenous RNA modules associated with clear cell kidney carcinoma.

Recent evidence has suggested that competitive endogenous RNAs (ceRNAs) are important regulatory molecules in clear cell kidney carcinoma (KIRC) and their dysregulation may contribute to cancer pathogenesis. However, the critical roles of dysregulated ceRNAs in KIRC remain unknown. In the present study, a KIRC dysregulated ceRNA­ceRNA network (KDCCNet) was constructed based on the 'ceRNA hypothesis' by integrating microRNA regulation and expression profiles in cancerous and normal tissues. Two dysregulated patterns of ceRNAs interaction (gain and loss) exist in KDCCNet. The two modules, which are 95% loss interactions and 97% gain interactions, were demonstrated to be able to distinguish normal samples from cancer samples. Two long non­coding (lnc)­RNAs (glucuronidase ß pseudogene 11 and LIFR antisense RNA 1) demonstrated significant associations with KIRC prognosis. The present study of the KDCCNet revealed a novel biological mechanism for KIRC and provides novel lncRNAs as candidate prognostic biomarkers.