Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, Shaanxi, China.
Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
ACS Appl Mater Interfaces. 2020 Mar 4;12(9):10156-10169. doi: 10.1021/acsami.0c00298. Epub 2020 Feb 20.
Burn infection is one of the commonest causes of death in severely burned patients. Developing multifunctional biological nanomaterials has a great significance for the comprehensive treatment of burn infection. In this paper, we developed a hydrogel-based nanodelivery system with antibacterial activity and skin regeneration function, which was used for photodynamic antimicrobial chemotherapy (PACT) in the treatment of burns. The treatment system is mainly composed of porphyrin photosensitizer sinoporphyrin sodium (DVDMS) and poly(lactic--glycolic acid) (PLGA)-encapsulated basic fibroblast growth factor (bFGF) nanospheres that are embedded in carboxymethyl chitosan (CMCS)-sodium alginate to form CSDP hybrid hydrogel. We systematically evaluated the inherent antibacterial performance, rheological properties, fluorescence imaging, and biocompatibility of the CSDP nanosystem. Under mild photoirradiation (30 J/cm, 5 min), 10 μg/mL CSDP showed excellent antibacterial and anti-biofilm activities, which eradicated almost 99.99% of and multidrug-resistant (MDR) in vitro. KEGG analysis identified that multiple signaling pathways were changed in MDR after PACT. In the burn-infection model, CSDP-PACT successfully inhibited bacteria growth and concurrently promoted wound healing. Moreover, several regenerative factors were increased and some proinflammatory factors were reduced in the burn wounds of CSDP hydrogel treatment. These results suggest that the multifunctional CSDP hydrogel is a portable, light-triggered, antibacterial theranostic-platform and CSDP-PACT provides a promising strategy or the mechanically based synergistic treatment of burn infections.
烧伤感染是严重烧伤患者死亡的最常见原因之一。开发多功能生物纳米材料对于烧伤感染的综合治疗具有重要意义。本文开发了一种具有抗菌活性和皮肤再生功能的水凝胶基纳米递药系统，用于光动力抗菌化疗（PACT）治疗烧伤。该治疗系统主要由卟啉类光敏剂血卟啉单甲醚（DVDMS）和包载碱性成纤维细胞生长因子（bFGF）的聚乳酸-羟基乙酸共聚物（PLGA）纳米球组成，这些纳米球嵌入羧甲基壳聚糖（CMCS）-海藻酸钠中形成 CSDP 杂化水凝胶。我们系统地评价了 CSDP 纳米系统的固有抗菌性能、流变性能、荧光成像和生物相容性。在温和的光照射（30 J/cm，5 min）下，10 μg/mL 的 CSDP 表现出优异的抗菌和抗生物膜活性，可在体外几乎消除 99.99%的 和耐多药 。KEGG 分析表明，PACT 后 MDR 的多个信号通路发生了变化。在烧伤感染模型中，CSDP-PACT 成功抑制了细菌生长，并同时促进了伤口愈合。此外，CSDP 水凝胶治疗的烧伤伤口中几种再生因子增加，一些促炎因子减少。这些结果表明，多功能 CSDP 水凝胶是一种便携式、光触发的抗菌治疗平台，CSDP-PACT 为烧伤感染的机械协同治疗提供了一种有前景的策略。
