一氧化碳（CO）是一种具有扩散性和生物膜渗透性的气体递质。然而，细胞外和细胞内的共同递送是否会产生相似或不同的生物功能的问题仍然没有解决。
近日，中国科学技术大学胡进明教授等人在Science China Materials发表研究论文，利用非金属共释放胶束作为局部CO递送的平台，系统地设计了不同尺寸、单体序列和壳层的胶束纳米颗粒。
本文要点
1) 在上述胶束中，只有被金黄色葡萄球菌（S. aureus）摄取并能够在细胞内共释放的胶束表现出有效的杀菌特性。2) 选择性杀菌作用与细胞内CO释放后羟基自由基的产生密切相关。3) 细胞内CO释放被证明可以有效治疗S. aureus引起的皮肤脓肿，且不需要额外的抗生素，显示出协同抗菌和抗炎作用。本研究证实了CO释放的空间位置对其抗菌性能具有重要影响，深化了对气体递质生理功能的理解和认识。Figure 1. (a) Schematic illustration of red light-triggered CO release from nonmetallic CO-releasing micelles for selective killing of S. aureus cells. (b) Antibacterial activities of CO-releasing micelles correlate with the sizes, monomer sequences, and shells of micellar nanoparticles. (c) Proposed antibacterial and anti-inflammatory mechanisms of nonmetallic CO-releasing micelles. The production of ·OH after intracellular CO release may contribute to bacterial death.![]()
Figure 2. (a) Intensity–average hydrodynamic distributions, f(Dh), of BP1-S, BP1-M, BP1-L, and BP1-EL micelles (100 μg mL−1) in PBS. (b) CO release profiles of BP1-S, BP1-M, BP1-L, and BP1-EL micelles (100 μg mL−1) in PBS with or without 650 nm irradiation (26 mW cm−2). (c) Bacterial viability of S. aureus bacteria after treatment with aqueous dispersions of BP1-S, BP1-M, BP1-L, and BP1-EL micelles with or without irradiation (650 nm, 26 mW cm−2, 30 min). (d) CLSM images of S. aureus after incubation with BP1-S and BP1-EL micelles. The bacteria are stained with FITC. The green and red channels were excited at 488 and 594 nm and collected at 510–540 (green) and 640–700 nm (red), respectively. (e) Bacterial viability of S. aureus cells after treatment with aqueous dispersions (5 μg mL−1) of BP1-S, BP1-M, BP1-L, and BP1-EL with or without irradiation (650 nm, 26 mW cm−2, 30 min). (f) Bacterial viability of S. aureus cells as a function of BP1 concentrations (5 and 25 μg mL−1) under irradiation (650 nm, 26 mW cm−2, 30 min). Data are presented as the mean ± s.d (n = 3). n.s. not significant; **p < 0.01, ****p < 0.0001.![]()
Figure 3. (a) Intensity–average hydrodynamic distributions, f(Dh), of RP1 (100 μg mL−1) in PBS. (b) CO release profiles of RP1 (100 μg mL−1) in PBS under 650 nm irradiation (26 mW cm−2). (c) Bacterial viability of S. aureus cells after treatment with aqueous dispersions of RP1 with or without irradiation (650 nm, 26 mW cm−2, 30 min). Data are presented as the mean ± s.d (n =3). n.s., not significant. (d) Schematic diagram showing the assembly of BP1 and RP1 copolymers. (e, f) Changes in the distances of the centers of mass between BP1/RP1 micelles and bilayer membranes, with their states shown in the insets.![]()
Figure 4. (a) Experimental timeline of the treatment of S. aureus-infected mice with CO-releasing BP1 micelles in a cutaneous abscess model. (b) Representative images of wound bed healing during the treatment (the diameter of rubber rings is 1 cm). (c) Bacterial colony-forming units separated from abscess tissues with varying treatments. (d) Histological analysis of abscess tissues with varying treatments on day 7. Quantification of inflammatory cytokine levels of (e) TNF-α, (f) IL-6, (g) IL-1β, and (h) IL-10 in serum with varying treatments on day 7. Data are presented as the mean ± s.d (n = 3). n.s., not significant, ****p < 0.0001.Tengfei Ma, Shaoqiu Zheng, Jian Cheng, Guoying Zhang, Jinming Hu. Intracellular carbon monoxide release unveils selective antibacterial effects. Sci. China Mater. (2024).https://doi.org/10.1007/s40843-024-2989-0
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