Abstract
BackgroundHealing 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 the treatment of diabetic wound healing, and in more severe cases it can even lead to amputation of the patient's limb.ResultsThe present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as a therapeutic nanoplatform for MIDBW to achieve the synergistic functions of NIR (near infrared)-response, ROS-generation, sterilization and promoted wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a stronger photocatalytic ability to produce singlet oxygen than BPQDs@H and the inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly 4-fold and basic fibroblast growth factor (bFGF) nearly 2-fold, which were beneficial for promoting 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 rat 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 obvious damage to rat major organs were observed.ConclusionsThe 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.