Zhang Fan, Li Qianqian, Dai Haibing, Li Weiqun, Chen Xiang, Wu Huibin, Lu Shanming, Luo Ran, Li Feng, Lu Guihong, Yu Jianbo, Mei Lin
Longgang Central Hospital, Shenzhen, Guangdong, 518100, China.
State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China.
Adv Sci (Weinh). 2025 Jun;12(22):e2417712. doi: 10.1002/advs.202417712. Epub 2025 Apr 25.
This study presents an innovative approach utilizing a biocompatible shell to shield bacterial outer membrane vesicles (OMVs) and incorporate Fe ions and ultrasmall Au nanoparticles to develop a combined tumor therapeutic strategy. These chimeric nanozyme shells effectively reduce the toxicity of OMVs during circulation and promote their accumulation in tumor tissues. In the tumor microenvironment, Au nanoparticles act as nanozymes, catalyzing glucose consumption and elevating H₂O₂ levels. The increased H₂O₂ subsequently reacts with the released Fe ions to induce immunogenic tumor cell death through iron-mediated chemodynamic mechanisms. Simultaneously, the release of tumor-associated antigens and OMVs synergistically stimulates the immune response. This cascade of nanozyme-catalyzed reactions, chemodynamic effects, and immune activation results in efficient tumor inhibition.
本研究提出了一种创新方法,利用生物相容性外壳来包裹细菌外膜囊泡(OMV),并掺入铁离子和超小金纳米颗粒,以开发一种联合肿瘤治疗策略。这些嵌合纳米酶外壳在循环过程中有效降低了OMV的毒性,并促进其在肿瘤组织中的积累。在肿瘤微环境中,金纳米颗粒作为纳米酶,催化葡萄糖消耗并提高过氧化氢水平。增加的过氧化氢随后与释放的铁离子反应,通过铁介导的化学动力学机制诱导免疫原性肿瘤细胞死亡。同时,肿瘤相关抗原和OMV的释放协同刺激免疫反应。这种由纳米酶催化反应、化学动力学效应和免疫激活组成的级联反应导致了有效的肿瘤抑制。