Biomimetic"Gemini nanoimmunoregulators"orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages

扫码查看

原文链接

NETL
NSTL
万方数据

外文摘要：A novel strategy of not only stimulating the immune cycle but also modulating the immuno-suppressive 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 nano-vectors 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 ampli-fied 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 im-mune evasion.Subsequently,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recog-nized 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 na-noimmunoregulators 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.

外文关键词：

Biomimetic immunoregulatorSpatiotemporal deliveryTargeted photothermal therapyAmplified immunogenic cell deathImmunosuppressive tumor microenvironmentPD-L1 degradationTAMs phenotype reversionMetastasis inhibition

作者：

Honglin Huang、Ningxi Li、Xiaodan Wei、Qingzhi Li、Junhan Guo、Geng Yang、Hong Yang、Lulu Cai、Yiyao Liu、Chunhui Wu

展开 >

作者单位：

Department of Pharmacy,Personalized Drug Therapy Key Laboratory of Sichuan Province,Sichuan Provincial People's Hospital,and School of Life Science and Technology,University of Electronic Science and Technology of China,Chengdu 610054,China

TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China

基金：

国家自然科学基金国家自然科学基金国家自然科学基金四川省科技计划四川省科技计划四川省科技计划Joint Funds of Center for Engineering MedicineJoint Funds of Center for Engineering MedicineJoint Funds of Center for Engineering Medicine

项目编号：

32171395U19A2006121320042021YJ01302022NSFSC00482023NSFSC0715ZYGX2021YGLH010ZYG-X2021YGLH017ZYGX2021YGLH204

出版年：

2024

DOI：

10.1016/j.apsb.2023.11.005

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(3)

参考文献量46