School of Materials Science & Engineering, South China University of Technology, Guangzhou 510006, China.
Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China.
ACS Nano. 2023 Mar 28;17(6):5740-5756. doi: 10.1021/acsnano.2c12165. Epub 2023 Mar 8.
Bacterial infection has been considered one of the primary reasons for low survival rate of lung cancer patients. Herein, we demonstrated that a kind of mesoporous silica nanoparticles loaded with anticancer drug doxorubicin (DOX) and antimicrobial peptide HHC36 (AMP) (MSN@DOX-AMP) can kill both commensal bacteria and tumor cells under GSH-triggering, modulating the immunosuppressive tumor microenvironment, significantly treating commensal bacterial infection, and eliminating lung tumors in a commensal model. Meanwhile, MSN@DOX-AMP encapsulated DOX and AMP highly efficiently a combined strategy of physical adsorption and click chemistry and exhibited excellent hemocompatibility and biocompatibility. Importantly, MSN@DOX-AMP could be inhaled and accumulate in lung by a needle-free nebulization, achieving a better therapeutic effect. This system is expected to serve as a straightforward platform to treat commensal bacterial infections in tumors and promote the translation of such inhaled GSH-triggered MSN@DOX-AMP to clinical treatments of lung cancer.
细菌感染被认为是导致肺癌患者生存率低的主要原因之一。在这里，我们证明了一种负载抗癌药物阿霉素（DOX）和抗菌肽 HHC36（AMP）的介孔硅纳米粒子（MSN@DOX-AMP）可以在 GSH 触发下杀死共生菌和肿瘤细胞，调节免疫抑制性肿瘤微环境，显著治疗共生菌感染，并在共生模型中消除肺肿瘤。同时，MSN@DOX-AMP 包封的 DOX 和 AMP 高效地采用物理吸附和点击化学的组合策略，表现出优异的血液相容性和生物相容性。重要的是，MSN@DOX-AMP 可以通过无针雾化吸入并在肺部积累，从而实现更好的治疗效果。该系统有望成为一种治疗肿瘤共生菌感染的简单平台，并促进这种吸入型 GSH 触发的 MSN@DOX-AMP 向肺癌临床治疗的转化。
