Spatiotemporally Controlled Bioorthogonal Prodrug Activation for Precise Chemotherapy.

ABSTRACT: The uncontrolled pharmacokinetics of anticancer drugs after systemic administration can cause off-target accumulation in healthy tissues, compromising the antitumor efficacy and posing serious safety issues. To address these limitations, the spatiotemporally controlled inverse electron demand Diels-Alder reaction (SC-IEDDA) strategy is developed, which controls bioorthogonal IEDDA reactions within tumor tissues for in situ prodrug activation and precise chemotherapy. The strategy employs two nanoplatforms: 1) pH-sensitive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles encapsulating trans-cyclooctene-caged doxorubicin (TCO-DOX, the prodrug) and 2) indocyanine green (ICG)-loaded near-infrared (NIR) light-responsive nanomicelles constructed from an amphiphilic molecule comprisi

SUBMITTER: Liu X 

PROVIDER: S-EPMC12798786 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature