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靶向生物膜的载氧水凝胶光动力与光热疗法联合抗菌及伤口愈合效果的研究

Research on the Combined Antibacterial and Wound-Healing Effects of Oxygen-Carrying Hydrogel Photodynamic and Photothermal Therapy-Targeting Biofilms.

作者信息

Zhang Weiwei, Yang Yongqi, Zhang Xuanjun, Song Ping, Shen Xiaokuo, Gui Lin, Zhu Longbao, Sun Dongdong, Ge Fei, Li Wanzhen

机构信息

School of Biological and Food Engineering, Anhui Polytechnic University, Wuhu, Anhui 241000, People's Republic of China.

Department of Microbiology and Immunology, Wannan Medical College, Wuhu, Anhui 241002, Peoples Republic of China.

出版信息

ACS Appl Mater Interfaces. 2025 Aug 25. doi: 10.1021/acsami.5c11868.

Abstract

Biofilms present a significant obstacle in the treatment of bacterial infections, because of their ability to evade the host immune response and to resist conventional antibacterial drugs. This study introduces an innovative approach to overcoming these challenges by targeting the biofilm microenvironment using a multifunctional therapeutic platform. The platform leverages perfluorohexane (PFH) as an oxygen carrier to alleviate the multifunctional therapeutic platform. It combines the photosensitizer indium Chlorin e6 (Ce6) and the photothermal agent molybdenum disulfide (MoS) co-encapsulated within a liposome nanoparticle structure, further stabilized by Zeolitic imidazolate framework-8 (ZIF-8). This configuration, termed MoS-Ce6-PFH@ZIF-8 (MCP@ZIF-8) improves the stability, functionality, and therapeutic potential of the nanoparticles. Additionally, the nanoparticles are embedded into a hydrogel matrix (MCP@ZCP formed by cross-linking carboxymethyl chitosan (CMCS) with pluronic F-127 (PF-127) for localized delivery. MCP@ZIF-8 exhibited a high photothermal therapy conversion efficiency of approximately 52.7%, thereby enabling effective heat generation under near-infrared (NIR) light. MCP@ZIF-8 produced higher reactive oxygen species levels than Ce6 alone under NIR irradiation at 660 nm. This dual photothermal and photodynamic mechanism achieves an antibacterial efficacy of up to 99%, effectively disrupting biofilms. Animal studies demonstrated that MCP@ZCP promotes superior wound healing, compared with conventional treatments. Transcriptome analysis demonstrated that MCP@ZCP disrupts bacterial metabolic pathways including amino acid synthesis, carbon metabolism, nitrogen metabolism, and other pathways, thereby inhibiting bacterial growth and proliferation. Comprehensive biosafety assessments have confirmed that MCP@ZCP is biocompatible and nontoxic, indicating its suitability for clinical applications. Thus, oxygen-carrying hydrogels can be used as an approach for treating bacterial infections.

摘要

生物膜在细菌感染治疗中构成了重大障碍,因为它们能够逃避宿主免疫反应并抵抗传统抗菌药物。本研究引入了一种创新方法,通过使用多功能治疗平台靶向生物膜微环境来克服这些挑战。该平台利用全氟己烷(PFH)作为氧载体来减轻多功能治疗平台的负担。它将光敏剂二氢卟吩铟e6(Ce6)和光热剂二硫化钼(MoS)共包封在脂质体纳米颗粒结构中,并通过沸石咪唑酯骨架-8(ZIF-8)进一步稳定。这种配置称为MoS-Ce6-PFH@ZIF-8(MCP@ZIF-8),提高了纳米颗粒的稳定性、功能性和治疗潜力。此外,纳米颗粒被嵌入水凝胶基质(通过羧甲基壳聚糖(CMCS)与普朗尼克F-127(PF-127)交联形成的MCP@ZCP)中进行局部递送。MCP@ZIF-8表现出约52.7%的高光热治疗转换效率,从而能够在近红外(NIR)光下有效产热。在660nm的NIR照射下,MCP@ZIF-8产生的活性氧水平比单独的Ce6更高。这种光热和光动力双重机制实现了高达99%的抗菌效果,有效破坏生物膜。动物研究表明,与传统治疗相比,MCP@ZCP促进了更好的伤口愈合。转录组分析表明,MCP@ZCP破坏了包括氨基酸合成、碳代谢、氮代谢等在内的细菌代谢途径,从而抑制细菌生长和增殖。全面的生物安全性评估证实MCP@ZCP具有生物相容性且无毒,表明其适用于临床应用。因此,载氧水凝胶可作为治疗细菌感染的一种方法。

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