Preparation of NIR-responsive, ROS-generating and antibacterial black phosphorus quantum dots for promoting the MRSA-infected wound healing in diabetic rats.

Multidrug-resistant (MDR) bacteria-induced infection is becoming a huge challenge for clinical treatment, especially for non-healing diabetic wound infections, which increase patient mortality. MRSA infections and delayed wound healing (methicillin-resistant Staphylococcus aureus) accounted for a higher proportion. Although surgical debridement and continuous use of antibiotics are still the main clinical treatments, new multifunctional therapeutic nanoplatform are attractive for MIDW. Thus, in the present study, black phosphorus quantum dots (BPQDs) encapsulated in hydrogel (BPQDs@NH) were utilized as nanoplatforms for MIDW treatment to achieve the multifunctional properties of NIR (near infrared) responsiveness, ROS (reactive oxygen species) generation and antibacterial activity. Upon NIR irradiation, the temperature of the BPQDs@NH-treated MIDW area rapidly increased up to 55 °C for sterilization. In vitro experiments showed that BPQDs@NH exerted a synergistic effect on inhibiting MRSA by producing of ROS, lipid peroxidation, glutathione, adenosine triphosphate accumulation and bacterial membrane destruction upon NIR irradiation. The resulting BPQDs@NH achieved an effective sterilization rate of approximately 90% for MRSA. Furthermore, animal experiments revealed that BPQDs@NH achieved an effective closure rate of 95% for MIDW after 12 days by reducing the inflammatory response and regulating the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Meanwhile, intravenous circulation experiments showed good biocompatibility of BPQDs, and no obvious damage to rat major organs was observed. The obtained results indicated that BPQDs@NH achieved the synergistic functions of NIR-responsiveness, ROS generation, and antibacterial activity and promoted wound healing, suggesting that they are promising multifunctional nanoplatforms for MIDW healing. STATEMENT OF SIGNIFICANCE: 1. NIR-triggered ROS-generating and antibacterial nanoplatforms are attractive in the wound healing field. 2. In this work, black phosphorus quantum dots encapsulated in a hydrogel were used as a nanoplatform for treating MRSA infected wounds. 3. The obtained materials have achieved an effective sterilization rate for MRSA and effective wound closure rate.

Tea polyphenol modified, photothermal responsive and ROS generative black phosphorus quantum dots as nanoplatforms for promoting MRSA infected wounds healing in diabetic rats.

BACKGROUND: Healing of MRSA (methicillin-resistant Staphylococcus aureus) infected deep burn wounds (MIDBW) in diabetic patients remains an obstacle but is a cutting-edge research problem in clinical science. Surgical debridement and continuous antibiotic use remain the primary clinical treatment for MIDBW. However, suboptimal pharmacokinetics and high doses of antibiotics often cause serious side effects such as fatal complications of drug-resistant bacterial infections. MRSA, which causes wound infection, is currently a bacterium of concern in diabetic wound healing. In more severe cases, it can even lead to amputation of the patient's limb. The development of bioactive nanomaterials that can promote infected wound healing is significant. RESULTS: The present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as therapeutic nanoplatforms for MIDBW to achieve the synergistic functions of NIR (near-infrared)-response, ROS-generation, sterilization, and promoting wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a more vital photocatalytic ability to produce singlet oxygen than BPQDs@H. The inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly fourfold and basic fibroblast growth factor (bFGF) nearly twofold, which were beneficial for promoting the proliferation of vascular endothelial cells and skin epidermal cells. Under NIR irradiation, EGCG-BPQDs hydrogel (EGCG-BPQDs@H) treated MIDBW area could rapidly raise temperature up to 55 °C for sterilization. The MIBDW closure rate of rats after 21 days of treatment was 92.4%, much better than that of 61.1% of the control group. The engineered EGCG-BPQDs@H were found to promote MIDBW healing by triggering the PI3K/AKT and ERK1/2 signaling pathways, which could enhance cell proliferation and differentiation. In addition, intravenous circulation experiment showed good biocompatibility of EGCG-BPQDs@H. No significant damage to major organs was observed in rats. CONCLUSIONS: The obtained results demonstrated that EGCG-BPQDs@H achieved the synergistic functions of photocatalytic property, photothermal effects and promoted wound healing, and are promising multifunctional nanoplatforms for MIDBW healing in diabetics.

Zinc attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury by activating Nrf2/GPX4 defense pathway.

AIM: Spinal cord injury (SCI) involves multiple pathological processes. Ferroptosis has been shown to play a critical role in the injury process. We wanted to explore whether zinc can inhibit ferroptosis, reduce inflammation, and then exert a neuroprotective effect. METHODS: The Alice method was used to establish a spinal cord injury model. The Basso Mouse Scale (BMS), Nissl staining, hematoxylin-eosin staining, and immunofluorescence analysis were used to investigate the protective effect of zinc on neurons on spinal cord neurons and the recovery of motor function. The regulation of the nuclear factor E2/heme oxygenase-1 (NRF2/HO-1) pathway was assessed, the levels of essential ferroptosis proteins were measured, and the changes in mitochondria were confirmed by transmission electron microscopy and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining. In vitro experiments using VSC4.1 (spinal cord anterior horn motor neuroma cell line), 4-hydroxynonenal (4HNE), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), lipid peroxides, and finally the levels of inflammatory factors were detected to assess the effect of zinc. RESULTS: Zinc reversed behavioral and structural changes after SCI. Zinc increased the expression of NRF2/HO-1, thereby increasing the content of glutathione peroxidase 4 (GPX4), SOD, and GHS and reducing the levels of lipid peroxides, MDA, and ROS. Zinc also rescued injured mitochondria and effectively reduced spinal cord injury and the levels of inflammatory factors, and the NRF2 inhibitor Brusatol reversed the effects of zinc. CONCLUSION: Zinc promoted the degradation of oxidative stress products and lipid peroxides through the NRF2/HO-1 and GPX4 signaling pathways to inhibit ferroptosis in neurons.

Preparation of ROS active and photothermal responsive hydroxyapatite nanoplatforms for anticancer therapy.

Photothermal responsive nanoplatforms are attracting for photothermal therapy (PTT) of cancer. Herein, we propose a strategy to prepare IR-780 modified hydroxyapatite (HAP) nanorods as photothermic agents (HAP@IR-780). The results demonstrated that the obtained HAP@IR-780 was photothermal responsive under near-infrared laser irradiation the photothermal conversion efficiency was 69.3%, and it remained photostability after 4 cycles of irradiation. This advantage overcomes the optical instability of IR780. MTT and cellular uptake research proved that HAP@IR-780 was biocompatible in appropriate concentration range (0-20 µg/mL) without laser irradiation. Concentration-dependent internalization and reactive oxygen species (ROS) related apoptosis of HAP@IR-780 for MCF-7 cells were observed. Animal experiments showed that the gathered HAP@IR-780 at the tumor site reached a photothermal responsive temperature up to 57.9 °C, which could almost ablate the tumor with volumes as large as 1500 mm3. In general, our photothermal material has good photothermal conversion characteristics, and may have the least safety problems while showing excellent therapeutic effects. Therefore, HAP@IR-780 has a brilliant prospect in the field of tumor photothermal therapy.