Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, P. R. China.
Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, P. R. China.
ACS Appl Mater Interfaces. 2023 Mar 1;15(8):10520-10528. doi: 10.1021/acsami.2c22937. Epub 2023 Feb 16.
The long-standing misuse of antibiotics has accelerated the emergence of drug-resistant bacteria, which gives rise to an urgent public health threat. Antibacterial photodynamic therapy (aPDT), as a burgeoning and promising antibacterial strategy, plays an essential role in avoiding the evolution of drug-resistant microbes. However, it is hard for conventional photosensitizers to achieve satisfactory antibacterial efficacy because of the complex bacterial infectious microenvironment (BIME). Herein, a cascade BIME-triggered near-infrared cyanine () nanoplatform has been developed via conjugating cyanine units to biocompatible hyaluronic acid (HA) for enhanced aPDT efficacy. The nanoparticles can be dissociated under the overexpressed hyaluronidase in BIME to release a cyanine photosensitizer. Meanwhile, cyanine can be protonated under acidic BIME, where protonated cyanine can efficiently adhere to the surface of a negatively charged bacterial membrane and increase singlet oxygen production due to intramolecular charge transfer (ICT). Experiments in the cellular level and animal model proved that the BIME-triggered activation of aPDT could remarkably boost aPDT efficacy. Overall, this BIME-triggered nanoplatform presents great promise for overcoming the dilemma of drug-resistant microbes.
长期滥用抗生素加速了耐药细菌的出现，这对公共健康构成了紧迫威胁。光动力抗菌疗法（aPDT）作为一种新兴且有前途的抗菌策略，在避免耐药微生物进化方面发挥着重要作用。然而，由于复杂的细菌感染微环境（BIME），传统的光敏剂很难实现令人满意的抗菌效果。在此，通过将氰基单元连接到生物相容性透明质酸（HA）上，开发了一种级联 BIME 触发的近红外菁（）纳米平台，以提高 aPDT 效果。纳米颗粒可以在 BIME 中过表达的透明质酸酶下解离，释放出一种氰基光敏剂。同时，氰基在酸性 BIME 下可以质子化，质子化的氰基可以由于分子内电荷转移（ICT）有效地粘附在带负电荷的细菌膜表面，并增加单线态氧的产生。细胞水平和动物模型的实验证明，BIME 触发的 aPDT 激活可以显著提高 aPDT 效果。总的来说，这种 BIME 触发的纳米平台为克服耐药微生物的困境带来了很大的希望。
