Aminopeptidase-Responsive NIR Photosensitizer for Precision Targeting and Eradication of Pseudomonas aeruginosa Biofilms

IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY ACS Applied Materials & Interfaces Pub Date : 2024-12-23 DOI:10.1021/acsami.4c16028
Yang Liu, Kaixuan Liu, Ling lei, Qinghua Wang, Xiang Wang, Xiangchuan Meng, Qian Liu, Jiacheng Du, Leilei Zhang, Marc Nazaré, Hai-Yu Hu
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Abstract

The emergence of resistance in Pseudomonas aeruginosa represents a significant global health challenge, particularly due to the hurdle of effectively penetrating biofilms with antimicrobials. Moreover, the rise of antibiotic-resistant pathogens has driven the urgent need for developing innovative therapeutic approaches to overcome antibiotic resistance. Antibacterial phototherapy strategies have shown great potential for combating pathogens due to their broad-spectrum antimicrobial activity, spatiotemporal controllability, and relatively low rate of resistance emergence. However, due to the lack of bacterial specificity and penetration, photosensitizers cause considerable damage to mammalian cells and normal tissues and are less effective against bacterial biofilms. Herein, we developed a novel dual-targeting antibacterial strategy to construct a near-infrared photosensitizer, Cy-NEO-Leu. Cy-NEO-Leu showed great bacterial targeting affinity, penetrating and accumulating in biofilms. At the site of infection, it was specifically activated by P. aeruginosa aminopeptidase (PaAP), producing Cy-NEO-NH2, which demonstrated outstanding photothermal (PTT) and photodynamic (PDT) properties, with a photothermal conversion efficiency of up to 70.34%. Both in vitro and in vivo results demonstrated that Cy-NEO-Leu significantly reduced the biofilm biomass and bacterial viability in P. aeruginosa biofilms. Moreover, phototherapy with Cy-NEO-Leu further activated the immune system, enhancing therapeutic efficacy and promoting wound healing. RNA-seq analysis revealed that the antibacterial mechanism of Cy-NEO-Leu-mediated phototherapy involves disruption of the transcriptional and translational processes of P. aeruginosa under laser irradiation. Overall, our results present a promising therapeutic approach against P. aeruginosa biofilms and inspire the development of next-generation antimicrobials.

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来源期刊
ACS Applied Materials & Interfaces
ACS Applied Materials & Interfaces 工程技术-材料科学:综合
CiteScore
16.00
自引率
6.30%
发文量
4978
审稿时长
1.8 months
期刊介绍: ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.
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