Qi Ye, Ren Shuangsong, Ye Junwei, Tian Yiming, Wang Guangyao, Zhang Siqi, Du Linyao, Li Yachen, Che Ying, Ning Guiling
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, Dalian, Liaoning 116024, PR China.
Department of Ultrasound, The First Affiliated Hospital of Dalian Medical University, 193 Lianhe Road, Dalian, Liaoning 116011, PR China.
Acta Biomater. 2022 Apr 15;143:445-458. doi: 10.1016/j.actbio.2022.02.034. Epub 2022 Feb 27.
The development of intelligent designs of new antibacterial modalities for diagnosing and treating chronic multidrug-resistant bacterial infections is an urgent need, but achieving the precisive theranostic in response to specific inflammatory microenvironments remains a great challenge. This paper describes our work designing and demonstrating infection microenvironment-activated core-shell Gd-doped BiS@Cu(II) boron imidazolate framework (BiS:Gd@Cu-BIF) nanoassemblies. Upon exposure to a single beam of 808 nm laser, BiS:Gd@Cu-BIF nanoassemblies showed exceptional photothermal conversion (η = 52.6%) and produced several cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, by depleting the intracellular glutathione and in-situ catalyzing the decomposition of endogenous hydrogen peroxide in the inflammatory microenvironment. The broad-spectrum antibacterial properties of nanoassemblies were confirmed to be effective against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) with an inhibition rate of 99.99% in vitro. Additionally, in vivo wound-healing studies revealed that BiS:Gd@Cu-BIF nanoassemblies could serve as an effective wound spray to accelerate healing following MRSA infections via photothermal/chemodynamic (PTT/CDT) synergistic therapy. The effective wound healing rate in the synergistic treatment group was 99.8%, which is higher than the 69.5% wound healing rate in the control group. Furthermore, magnetic resonance and computed tomography dual-modal imaging mediated by BiS:Gd@Cu-BIF nanoassemblies also exhibits promising potential as an integrated diagnostic nanoplatform. Overall, this work provides useful insights for developing all-in-one theranostic nanoplatforms for clinical treatment of drug-resistant bacterial infections. STATEMENT OF SIGNIFICANCE: New treatments and effective diagnostic strategies are critical for fighting drug-resistant bacterial infections. Infection microenvironment-activated BiS@Cu-BIF nanoassemblies can simultaneously increase eigen temperature and generate cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, under near-infrared laser irradiation, achieving the synergistic effect of photothermal and chemodynamic therapy, which has been proven to be highly effective for inhibiting bacterial activity and speeding wound healing from methicillin-resistant Staphylococcus aureus infection. More importantly, the nanoassemblies could enable early precise visualized detection of bacterial abscess using magnetic resonance/computed tomography dual-modal bio-imaging techniques.
开发用于诊断和治疗慢性多重耐药细菌感染的新型抗菌模式的智能设计迫在眉睫，但要实现针对特定炎症微环境的精确诊疗仍面临巨大挑战。本文描述了我们设计并展示感染微环境激活的核壳型钆掺杂硫化铋@铜（II）硼咪唑框架（BiS:Gd@Cu-BIF）纳米组装体的工作。在暴露于一束808纳米激光时，BiS:Gd@Cu-BIF纳米组装体表现出卓越的光热转换性能（η = 52.6%），并通过消耗细胞内谷胱甘肽和在炎症微环境中原位催化内源性过氧化氢分解，产生了几种细胞毒性活性氧，如单线态氧和羟基自由基。纳米组装体的广谱抗菌性能经证实对大肠杆菌和耐甲氧西林金黄色葡萄球菌有效，在体外抑制率达99.99%。此外，体内伤口愈合研究表明，BiS:Gd@Cu-BIF纳米组装体可作为一种有效的伤口喷雾剂，通过光热/化学动力学（PTT/CDT）协同疗法加速耐甲氧西林金黄色葡萄球菌感染后的伤口愈合。协同治疗组的有效伤口愈合率为99.8%，高于对照组的69.5%。此外，由BiS:Gd@Cu-BIF纳米组装体介导的磁共振和计算机断层扫描双模态成像作为一种集成诊断纳米平台也展现出了广阔前景。总体而言，这项工作为开发用于临床治疗耐药细菌感染的一体化诊疗纳米平台提供了有益见解。重要意义声明：新的治疗方法和有效的诊断策略对于对抗耐药细菌感染至关重要。感染微环境激活的BiS@Cu-BIF纳米组装体在近红外激光照射下可同时升高自身温度并产生细胞毒性活性氧，如单线态氧和羟基自由基，实现光热和化学动力学疗法的协同效应，已被证明对抑制细菌活性和加速耐甲氧西林金黄色葡萄球菌感染的伤口愈合非常有效。更重要的是，纳米组装体能够利用磁共振/计算机断层扫描双模态生物成像技术对细菌脓肿进行早期精确可视化检测。
