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Herein, the photosensitizer rhodamine derivatives are selected as the light\u2010trapping dye and the electron\u2010rich substituent N\u2010nitrosoaminophen as the nitric oxide (NO)\u2010releasing component to develop a multifunctional (deep) red\u2010light activatable NO photocage\/photodynamic prodrug for efficient treatment of wounds and diabetic foot infections. The prodrug, RhB\u2010NO\u20102 integrates antimicrobial photodynamic therapy (aPDT), NO sterilization, and NO\u2010mediated anti\u2010inflammatory properties within a small organic molecule and is capable of releasing NO and generating Reactive oxygen species (ROS) when exposed to (deep) red laser (660\u00a0nm). This strategy overcomes the limitation of using a single photosensitizer, which is often inadequate for eliminating drug\u2010resistant bacteria. Additionally, it demonstrates that NO released from the prodrug can interact with superoxide anions (O<jats:sub>2<\/jats:sub><jats:sup>\u2022\u2212<\/jats:sup>) generated by PDT to form a more reactive and oxidative agent, peroxynitrite (ONOO<jats:sup>\u2212<\/jats:sup>). These three components act synergistically to enhance the antimicrobial effects. Furthermore, the released NO can inhibit the NF\u2010\u03baB pathway by regulating the expression of toll\u2010like receptor 2 (TRL2) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), thereby alleviating tissue inflammation. The developed prodrug \uff0c RhB\u2010NO\u20102 has the potential to expedite the healing of superficial infected wounds and offer a promising approach for treating diabetic foot ulcers (DFUs).<\/jats:p>","DOI":"10.1002\/smll.202408759","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T08:06:14Z","timestamp":1736409974000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Deep Red\u2010Light\u2010Mediated Nitric Oxide and Photodynamic Synergistic Antibacterial Therapy for the Treatment of Drug\u2010Resistant Bacterial Infections"],"prefix":"10.1002","volume":"21","author":[{"given":"Jingjing","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering School of Engineering China Pharmaceutical University  639 Longmian Road, Jiangning Nanjing 210009 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