Jinzhou Medical University, Jinzhou, 121001, Liaoning, China.
J Nanobiotechnology. 2021 Nov 10;19(1):362. doi: 10.1186/s12951-021-01106-w.
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.
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.
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.
糖尿病患者的耐甲氧西林金黄色葡萄球菌（MRSA）感染深度烧伤创面（MIDBW）的愈合仍然是一个障碍，但这是临床科学中的一个前沿研究问题。外科清创术和持续使用抗生素仍然是 MIDBW 的主要临床治疗方法。然而，抗生素药代动力学不理想和高剂量常常导致严重的副作用，如致命的耐药细菌感染并发症。引起伤口感染的 MRSA 目前是糖尿病伤口愈合中值得关注的细菌。在更严重的情况下，甚至可能导致患者肢体截肢。开发能够促进感染性伤口愈合的生物活性纳米材料具有重要意义。
本工作提出了一种策略，即使用 EGCG（表没食子儿茶素没食子酸酯）修饰黑磷量子点（BPQDs）作为 MIDBW 的治疗性纳米平台，以实现近红外（NIR）响应、ROS 产生、杀菌和促进伤口愈合的协同功能。电子顺磁共振结果表明，EGCG-BPQDs@H 比 BPQDs@H 具有更重要的光催化能力来产生单线态氧。抑制结果表明，对 MRSA 的有效杀菌率为 88.6%。分子生物学分析表明，EGCG-BPQDs 可使 CD31 显著上调近 4 倍，碱性成纤维细胞生长因子（bFGF）上调近 2 倍，有利于促进血管内皮细胞和皮肤表皮细胞的增殖。在近红外照射下，EGCG-BPQDs 水凝胶（EGCG-BPQDs@H）处理的 MIDBW 区域可迅速将温度升高至 55°C 以进行杀菌。治疗 21 天后，大鼠的 MIDBW 闭合率为 92.4%，明显优于对照组的 61.1%。研究结果表明，工程化的 EGCG-BPQDs@H 通过触发 PI3K/AKT 和 ERK1/2 信号通路促进 MIDBW 愈合，从而增强细胞增殖和分化。此外，静脉循环实验表明 EGCG-BPQDs@H 具有良好的生物相容性。在大鼠中未观察到主要器官的明显损伤。
研究结果表明，EGCG-BPQDs@H 实现了光催化性能、光热效应和促进伤口愈合的协同功能，是糖尿病患者 MIDBW 愈合有前途的多功能纳米平台。
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