前药
胶束
兴奋剂
药理学
免疫疗法
癌症研究
药品
干扰素基因刺激剂
材料科学
刺
免疫系统
医学
化学
免疫学
先天免疫系统
内科学
受体
物理化学
水溶液
工程类
航空航天工程
作者
Mengqi Chen,Chunhong Wang,Xuanyu Wang,Zhiyu Tu,Zexuan Ding,Zhibo Liu
标识
DOI:10.1002/adma.202307818
摘要
Materials that can respond to multiple biomarkers simultaneously, acting as an "AND" gate, have the potential to enhance tumor-targeting for drug delivery. In this study, an "AND" logic-controlled release prodrug micelle is developed for codelivering the chemotherapeutic and the stimulator of interferon genes (STING) agonist, enabling precise combinatorial therapy. The drug release is programmed by tumor-enriched boramino acids (BAA) in the tumor microenvironment and intracellular reactive oxygen species (ROS), resulting in enhanced tumor targeting. STING agonist is successfully encapsulated into prodrug micelles through π-π stacking and hydrophobic interactions. These AND logic-gated prodrug micelles can achieve tumor-targeted delivery of STING agonist, leading to significantly enhanced immune activation and antitumor efficacy in vivo. It is expected that this clinically relevant nanoplatform will provide a rational design of an effective immunotherapy combination regimen to convert immunologically "cold" tumors to immunogenic "hot" tumors, addressing the major challenges faced by immunotherapies.
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