PDF(Pubmed)
Abstract：
Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 → •O2- and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.
摘要：
乳酸（LA）在肿瘤微环境中的积累对有效的肿瘤免疫治疗提出了显着挑战。这里,提出了一种基于非典型Veillonella（VA）独特的生理结构和代谢特征的智能肿瘤治疗微型机器人，通过点击化学反应将金黄色葡萄球菌细胞膜包覆的BaTiO3纳米管（SAM@BTO）负载在VA细胞（VA-SAM@BTO）表面。口服后，VA-SAM@BTO通过SAM的炎症靶向和VA的低氧靶向准确靶向原位结直肠癌。在体外超声刺激下，BTO催化两个还原反应（O2→·O2-和CO2→CO）和三个氧化反应（H2O→·OH，GSH→GSSG,和LA→PA)同时，有效诱导肿瘤细胞的免疫原性死亡。BTO催化VA细胞代谢LA的氧化偶联，有效破坏免疫抑制微环境，改善树突状细胞成熟和巨噬细胞M1极化，增加效应T细胞比例，同时减少调节性T细胞数量，这有利于协同催化和免疫疗法。
