Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin, University, Tianjin 300350, China.
Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China.
Biomater Sci. 2023 Sep 12;11(18):6236-6251. doi: 10.1039/d3bm00774j.
With an increasing proportion of drug-resistant bacteria, photothermal therapy (PTT) is a promising alternative to antibiotic treatment for infected diabetic skin ulcers. However, the inevitable thermal damage to the tissues restricts its clinical practice. Carbon monoxide (CO), as a bioactive gas molecule, can selectively inhibit bacterial growth and promote tissue regeneration, which may be coordinated with PTT for drug-resistant bacteria killing and tissue protection. Herein, a CO-mediated PTT agent (CO@mPDA) was engineered by loading manganese carbonyl groups into mesoporous polydopamine (mPDA) nanoparticles coordination interactions between the metal center and a catechol group. Compared to the traditional PTT, the CO-mediated PTT increases the inhibition ratio of the drug-resistant bacteria both and in diabetic wound beds by selectively inhibiting the co-chaperone of the heat shock protein 90 kDa (Hsp90), and lowers the heat resistance of the bacteria rather than the mammalian tissues. Meanwhile, the tissue-protective proteins, such as Hsp90 and vimentin (Vim), are upregulated the WNT and PI3K-Akt pathways to reduce thermal injury, especially with a laser with a high-power density. The CO-mediated PTT unified the bacterial killing with tissue protection, which offers a promising concept to improve PTT efficiency and minimize the side-effects of PTT when treating infected skin wounds.
随着耐药菌比例的增加，光热疗法（PTT）是治疗感染性糖尿病皮肤溃疡的一种有前途的抗生素替代疗法。然而，组织不可避免的热损伤限制了其临床应用。一氧化碳（CO）作为一种生物活性气体分子，可以选择性地抑制细菌生长并促进组织再生，这可能与 PTT 协同作用，以杀死耐药菌并保护组织。本文通过将羰基锰负载到介孔聚多巴胺（mPDA）纳米粒子中，构建了一种 CO 介导的 PTT 试剂（CO@mPDA），金属中心与儿茶酚基团之间存在配位相互作用。与传统 PTT 相比，CO 介导的 PTT 通过选择性抑制热休克蛋白 90 kDa（Hsp90）的共伴侣，增加了耐药菌和糖尿病伤口床的抑制率，并降低了细菌的耐热性，而不是哺乳动物组织的耐热性。同时，组织保护蛋白，如 Hsp90 和波形蛋白（Vim），通过上调 WNT 和 PI3K-Akt 通路来增加，以减少热损伤，尤其是在高功率密度的激光下。CO 介导的 PTT 将细菌杀伤与组织保护统一起来，为提高 PTT 效率和最小化 PTT 治疗感染性皮肤伤口的副作用提供了一个有前途的概念。
