穿孔素
细胞毒性T细胞
材料科学
癌症免疫疗法
颗粒酶B
溶酶体
癌症研究
免疫疗法
细胞生物学
生物
免疫系统
生物化学
免疫学
酶
体外
作者
Qin Zhao,Zijian Gong,Zhihao Li,Jinyang Wang,Jinglun Zhang,Zifan Zhao,Peng Zhang,Shihang Zheng,Richard J. Miron,Quan Yuan,Yufeng Zhang
标识
DOI:10.1002/adma.202100616
摘要
T cell immunotherapy holds significant challenges in solid tumors, mainly due to the T cells' low activation and the decreased synthesis-release of therapeutic proteins, including perforin and granzyme B, which are present in lysosomes. In this study, a lysosome-targeting nanoparticle (LYS-NP) is developed by way of a mineralized metal-organic framework (MOF) coupled with a lysosome-targeting aptamer (CD63-aptamer) to enhance the antitumor effect of T cells. The MOF synthesized from Zn2+ and dimethylimidazole has good protein encapsulation and acid sensitivity, and is thus an ideal lysosomal delivery vector. Calcium carbonate (CaCO3 ) is used to induce MOF mineralization, improve the composite material's stability in encapsulating therapeutic protein, and provide calcium ions with synergistic effects. Before mineralization, perforin and granzyme B-T cell-needed therapeutic proteins for tumors-are preloaded with the MOF. Moreover, T cells are pretreated with processed tumor-specific antigens to activate or produce memory before reprogramming the lysosomes, facilitating the T cell receptor (TCR) for release of the therapeutic proteins. Using T cells recombined by LYS-NPs, a significant enhancement of breast cancer control is confirmed.
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