Multifunctional AIE Nanosphere-Based “Nanobomb” for Trimodal Imaging-Guided Photothermal/Photodynamic/Pharmacological Therapy of Drug-Resistant Bacterial Infections
Bin Li, Wei Wang, Lu Zhao, Dingyuan Yan, Xiaoxue Li, Qiuxia Gao, Judun Zheng, Sitong Zhou, Shanshan Lai, Yi Feng, Jie Zhang, Hang Jiang, Chengmin Long, Wenjun Gan, Xiaodong Chen, Dong Wang, Ben Zhong Tang, Yuhui Liao
Abstract
Injudicious or inappropriate use of antibiotics has led to the prevalence of drug-resistant bacteria, posing a huge menace to global health. Here, a self-assembled aggregation-induced emission (AIE) nanosphere (AIE-PEG 1000 NPs) that simultaneously possesses near-infrared region II (NIR-II) fluorescence emissive, photothermal, and photodynamic properties is prepared using a multifunctional AIE luminogen (AIE-4COOH). The AIE-PEG 1000 NPs were encapsulated with teicoplanin (Tei) and ammonium bicarbonate (AB) into lipid nanovesicles to form a laser-activated “nanobomb” (AIE-Tei@AB NVs) for the multimodal theranostics of drug-resistant bacterial infections. In vivo experiments validate that the “nanobomb” enables high-performance NIR-II fluorescence, infrared thermal, and ultrasound (AB decomposition during the photothermal process to produce numerous CO 2 /NH 3 bubbles, which is an efficient ultrasound contrast agent) imaging of multidrug-resistant bacteria-infected foci after intravenous administration of AIE-Tei@AB NVs followed by 660 nm laser stimulation. The highly efficient photothermal and photodynamic features of AIE-Tei@AB NVs, combined with the excellent pharmacological property of rapidly released Tei during bubble generation and NV disintegration, collectively promote broad-spectrum eradication of three clinically isolated multidrug-resistant bacteria strains and rapid healing of infected wounds. This multimodal imaging-guided synergistic therapeutic strategy can be extended for the theranostics of superbugs.