Photoinduced Unveiling of Cationic Amine: Toward Smart Photoresponsive Antimicrobial Polymers AITranslate

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DOI：https://doi.org/10.1021/acsapm.3c01904

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The growing number of infections caused by multidrug-resistant (MDR) bacteria is a cause for concern, and this global issue urgently needs the development of antimicrobial agents. Antimicrobial peptides (AMPs) and their mimics have emerged as promising candidates because of their ability to combat MDR bacteria with minimal resistance. However, this class of compounds still suffers from toxicity and selectivity issues due to the indiscriminate binding of cationic groups with mammalian cells. Herein, we report the development of a smart antimicrobial polymer with ortho-nitrobenzyl masking groups (PONB) that can be activated under ultraviolet (UV) light (300 nm) to unveil cationic primary amines and confer antimicrobial activity. The photoactivated polymer (PPhoto) exhibited bacteriostatic activity toward Gram-negative and -positive bacteria including MDR isolates obtained from eye infections, with minimum inhibitory concentration (MIC) values ranging from 30 to 61 μM. In addition, PPhoto was bactericidal against an MDR Pseudomonas aeruginosa strain, resulting in >3-log10 reduction of bacteria cells within 1 h of treatment. The membrane permeability assay confirmed that PPhoto could cause bacterial membrane disruption, which is typical of AMPs. Additionally, PPhoto could also disperse and kill biofilms of P. aeruginosa. Furthermore, PPhoto could kill HeLa cancer cells effectively, thus demonstrating the potential applicability of such a photoresponsive system for cancer therapy. In addition, toxicity studies verified that the masked prodrug polymer PONB had low hemolytic properties and was more biocompatible than the free cationic polymer PPhoto. This study thus lays the foundation for the development of smart photoresponsive antimicrobial (and anticancer) polymers as an attractive avenue to overcome toxicity and selectivity issues in biologically active polymers where the cationic character and subsequent biological activity can be switched on simply by using an external stimulus like light.