Yuwen Lihui, Xiao Huayu, Lu Pei, Chen Xiaolong, Li Jianguang, Xiu Weijun, Gan Siyu, Yang Dongliang, Wang Lianhui
State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China.
Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University, Nanjing 211816, China.
Biomater Sci. 2023 Jan 17;11(2):630-640. doi: 10.1039/d2bm01570f.
Effective treatment of bacterial biofilm-related infections is a great challenge for the medical community. During the formation of biofilms, bacteria excrete extracellular polymeric substances (EPS), including polysaccharides, proteins, nucleic acids, , to encapsulate themselves and form a "fort-like" structure, which greatly reduces the efficiency of therapeutic agents. Herein, we prepared a nanoagent (MnO-amylase-PEG-ICG nanosheets, MAPI NSs) with biofilm degradation capability for efficient photothermal therapy and fluorescence imaging of methicillin-resistant (MRSA) biofilm infections. MAPI NSs were constructed by sequentially modifying α-amylase, polyethylene glycol (PEG), and indocyanine green (ICG) on manganese dioxide nanosheets (MnO NSs). Experimental results exhibited that MAPI NSs could accumulate in infected tissues after intravenous injection, degrade in the acidic biofilm microenvironment, and release the loaded ICG for near-infrared (NIR) fluorescence imaging of the infected tissues. Importantly, MAPI NSs could efficiently eliminate MRSA biofilm infections in mice by α-amylase enhanced photothermal therapy. In addition, MAPI NSs exhibited neglectable toxicity towards mice. Given the superior properties of MAPI NSs, the enzyme-degradation enhanced therapeutic strategy presented in this work offers a promising solution for effectively combating biofilm infectious diseases.
有效治疗与细菌生物膜相关的感染对医学界来说是一项巨大挑战。在生物膜形成过程中，细菌分泌细胞外聚合物（EPS），包括多糖、蛋白质、核酸等，将自身包裹起来并形成一种“堡垒状”结构，这大大降低了治疗剂的疗效。在此，我们制备了一种具有生物膜降解能力的纳米剂（MnO-淀粉酶-聚乙二醇-吲哚菁绿纳米片，MAPI NSs），用于耐甲氧西林金黄色葡萄球菌（MRSA）生物膜感染的高效光热治疗和荧光成像。MAPI NSs是通过在二氧化锰纳米片（MnO NSs）上依次修饰α-淀粉酶、聚乙二醇（PEG）和吲哚菁绿（ICG）构建而成。实验结果表明，MAPI NSs静脉注射后可在感染组织中蓄积，在酸性生物膜微环境中降解，并释放负载的ICG用于感染组织的近红外（NIR）荧光成像。重要的是，MAPI NSs可通过α-淀粉酶增强的光热疗法有效消除小鼠体内的MRSA生物膜感染。此外，MAPI NSs对小鼠表现出可忽略不计的毒性。鉴于MAPI NSs的优异性能，本研究中提出的酶降解增强治疗策略为有效对抗生物膜感染性疾病提供了一种有前景的解决方案。
