肿瘤微环境
癌症研究
免疫疗法
免疫系统
癌症免疫疗法
细胞毒性T细胞
转移
T细胞
化学
癌症
医学
生物
免疫学
体外
肿瘤细胞
内科学
生物化学
作者
Haoliang Huang,Ningxi Li,Xiaodan Wei,Qingzhi Li,Junhan Guo,Geng Yang,Hong Yang,Lulu Cai,Yiyao Liu,Chunhui Wu
标识
DOI:10.1016/j.apsb.2023.11.005
摘要
A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy. Here, a new type of spatiotemporal biomimetic "Gemini nanoimmunoregulators" was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death (ICD), tumor-associated macrophages (TAMs) phenotype reprogramming and programmed cell death ligand 1 (PD-L1) degradation. The "Gemini nanoimmunoregulators" PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine (mPDA) as nanovectors to deliver metformin (Met) and toll-like receptor 7/8 agonist resiquimod (R848) to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane (RM) inlaid with T7 or M2 peptides. mPDA/Met@RM-T7 (abbreviated as PM@RM-T7) was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity. Meanwhile, PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion. Subsequently, mPDA/R848@RM-M2 (abbreviated as PR@RM-M2) specifically recognized TAMs and reset the phenotype from M2 to M1 state, thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes. This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity, which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis. This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.
科研通智能强力驱动
Strongly Powered by AbleSci AI