Acta Biomaterialia ( IF 9.4 ) Pub Date : 2023-03-11 , DOI: 10.1016/j.actbio.2023.03.008 Ting Du 1 , Zehui Xiao 1 , Guanghui Zhang 1 , Lifei Wei 1 , Jiangli Cao 1 , Zhannuo Zhang 1 , Xingxing Li 1 , Zhiyong Song 2 , Wenjing Wang 2 , Jifeng Liu 1 , Xinjun Du 1 , Shuo Wang 3
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Wound treatment is largely influenced by pre-existing hypoxic microenvironments and biofilms, which can severely diminish the efficacy of phototherapy, suggesting the importance of multifunctional nanoplatforms for synergistic treatment of wound infections. Here, we developed a multifunctional injectable hydrogel (PSPG hydrogel) by loading photothermal sensitive sodium nitroprusside (SNP) into Pt-modified porphyrin metal organic framework (PCN) and in situ modification of gold particles to form a near-infrared (NIR) light-triggered all-in-one phototherapeutic nanoplatform. The Pt-modified nanoplatform exhibits a remarkable catalase-like behavior and promotes the continuous decomposition of endogenous H2O2 into O2, thereby enhancing the photodynamic therapy (PDT) effect under hypoxia. Under dual NIR irradiation, PSPG hydrogel can not only produce hyperthermia (η=89.21%) but also generate reactive oxygen species and trigger NO release, contributing jointly to removal of biofilms and disruption of the cell membranes of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). In vivo experiments demonstrated a 99.9% reduction in bacterial burden on wounds. Additionally, PSPG hydrogel can accelerate MRSA-infected and Pseudomonas aeruginosa-infected (P. aeruginosa-infected) wound healing by promoting angiogenesis, collagen deposition, and suppressing inflammatory responses. Furthermore, in vitro and in vivo experiments revealed that PSPG hydrogel has good cytocompatibility. Overall, we proposed an antimicrobial strategy to eliminate bacteria through the synergistic effects of gas-photodynamic-photothermal killing, alleviating hypoxia in the bacterial infection microenvironment, and inhibiting biofilms, offering a new way against antimicrobial resistance and biofilm-associated infections.
Statement of significance
The NIR light-triggered multifunctional injectable hydrogel nanoplatform (PSPG hydrogel) based on Pt-decorated gold nanoparticles with sodium nitroprusside (SNP)-loading porphyrin metal organic framework (PCN) as inner templates can efficiently perform photothermal conversion (η=89.21%) to trigger NO release from SNP, while continuously regulating the hypoxic microenvironment at the bacterial infection site through Pt-induced self-oxygenation, achieving efficient sterilization and removal of biofilm by synergistic PDT and PTT phototherapy. In vivo and in vitro experiments demonstrated that the PSPG hydrogel has significant anti-biofilm, antibacterial, and inflammatory regulatory functions. This study proposed an antimicrobial strategy to eliminate bacteria through the synergistic effects of gas-photodynamic-photothermal killing, alleviating hypoxia in the bacterial infection microenvironment, and inhibiting biofilms.
中文翻译：
一种用于根除细菌生物膜和伤口愈合的可注射多功能水凝胶
伤口治疗在很大程度上受预先存在的缺氧微环境和生物膜的影响，这会严重降低光疗的疗效，这表明多功能纳米平台对于伤口感染协同治疗的重要性。在这里，我们开发了一种多功能可注射水凝胶（PSPG 水凝胶），通过将光热敏感的硝普钠（SNP）加载到 Pt 修饰的卟啉金属有机骨架（PCN）中并原位修饰金颗粒以形成近红外（NIR）光-触发多合一光疗纳米平台。Pt修饰的纳米平台表现出显着的类过氧化氢酶行为，促进内源性H2O2为O2，从而增强缺氧条件下的光动力疗法（PDT）效果。在双重 NIR 照射下，PSPG 水凝胶不仅可以产生高热 (η=89.21%)，还可以产生活性氧并触发 NO 释放，共同有助于去除生物膜和破坏耐甲氧西林金黄色葡萄球菌 (MRSA )的细胞膜和大肠杆菌( E. coli )。体内实验证明伤口细菌负担减少了 99.9%。此外，PSPG 水凝胶可以加速 MRSA 感染和铜绿假单胞菌感染（P. aeruginosa-infected) 伤口愈合通过促进血管生成、胶原蛋白沉积和抑制炎症反应。此外，体外和体内实验表明PSPG水凝胶具有良好的细胞相容性。总的来说，我们提出了一种抗菌策略，通过气体-光动力-光热杀灭的协同作用消除细菌，减轻细菌感染微环境中的缺氧，抑制生物膜，为对抗抗菌素耐药性和生物膜相关感染提供了一种新方法。
重要性声明
基于以硝普钠（SNP）负载卟啉金属有机骨架（PCN）为内模板的铂修饰金纳米粒子的近红外光触发多功能可注射水凝胶纳米平台（PSPG 水凝胶）可以有效地进行光热转换（η=89.21%）触发SNP释放NO，同时通过Pt诱导的自氧化持续调节细菌感染部位的缺氧微环境，通过协同PDT和PTT光疗实现高效杀菌和去除生物膜。体内和体外实验表明，PSPG水凝胶具有显着的抗生物膜、抗菌和炎症调节功能。该研究提出了一种抗菌策略，通过气体-光动力-光热杀灭的协同作用来消除细菌，缓解细菌感染微环境缺氧，抑制生物膜。
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