Liu Wenzhen, Zhang Yuxiang, You Wenwu, Su Jianqiang, Yu Shaohua, Dai Tao, Huang Yunmei, Chen Xueyuan, Song Xiaorong, Chen Zhuo
State Key Laboratory of Structural Chemistry, CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian College, University of Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
Nanoscale. 2020 Jul 14;12(26):13948-13957. doi: 10.1039/d0nr01073a. Epub 2020 May 12.
Extensively drug-resistant Acinetobacter baumannii (XDR-AB) has raised considerable concerns due to its mortal damage to humans and its high transmission rate of infections in hospitals. However, current antibiotics not only show poor anti-infection effects in vivo but also frequently cause high nephrotoxicity and neurotoxicity. Herein, we report a near-infrared (NIR) light-initiated antimicrobial photodynamic therapy (aPDT) to effectively treat in vivo XDR-AB infections based on photosensitizer (PS) loaded upconversion nanoparticles (UCNPs, LiYF:Yb/Er). Such nanoagents feature robust NIR triggered UC luminescence and high-efficiency energy transfer from UCNPs to the loaded PS, thereby allowing NIR-triggered generation of reactive oxygen species (ROS) for destroying the bacterial cell membrane. This strategy permits a high antibacterial activity against XDR-AB, resulting in a decline of 4.72 log in viability at a dose of 50 μg mL UCNPs-PVP-RB with 980 nm laser irradiation (1 W cm). More significantly, we can achieve excellent therapeutic efficacy against deep-tissue (about 5 mm) XDR-AB infections without causing any side effects in the murine model. In brief, such NIR-activated aPDT may open up new avenues for treating various deep-tissue intractable infections.
广泛耐药鲍曼不动杆菌（XDR-AB）因其对人类的致命危害以及在医院中高感染传播率而引发了广泛关注。然而，目前的抗生素不仅在体内抗感染效果不佳，还经常导致高肾毒性和神经毒性。在此，我们报道了一种基于负载光敏剂（PS）的上转换纳米颗粒（UCNPs，LiYF:Yb/Er）的近红外（NIR）光引发抗菌光动力疗法（aPDT），以有效治疗体内XDR-AB感染。这种纳米制剂具有强大的近红外触发上转换发光以及从UCNPs到负载PS的高效能量转移，从而实现近红外触发产生活性氧（ROS）以破坏细菌细胞膜。该策略对XDR-AB具有高抗菌活性，在980 nm激光照射（1 W/cm²）下，50 μg/mL UCNPs-PVP-RB剂量可使细菌存活率下降4.72个对数级。更重要的是，在小鼠模型中，我们能够对深部组织（约5 mm）XDR-AB感染实现优异的治疗效果且不产生任何副作用。简而言之，这种近红外激活的aPDT可能为治疗各种深部组织难治性感染开辟新途径。
