An "AND" Logic-Gated Prodrug Micelle Locally Stimulates Anti-Tumor Immunity.

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 co-delivering the chemotherapeutic and the 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 nano-platform 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. This article is protected by copyright. All rights reserved.