A Reactivity‐Tunable Self‐Immolative Design Enables Histone Deacetylase‐Targeted Imaging and Prodrug Activation

作者：Feng Liu, Xu Ding, Xiaobo Xu, Fenglin Wang, Xia Chu, Jian‐Hui Jiang · 发表于：Angewandte Chemie International Edition · 年份：2022 · DOI：10.1002/anie.202203243 · 被引用次数：25 · 研究领域：Nanoplatforms for cancer theranostics、RNA Interference and Gene Delivery、Histone Deacetylase Inhibitors Research

Histone deacetylase (HDAC)-targeted probes and prodrugs are crucial for cancer theranostics. We developed a self-immolative design that enables in vivo activatable near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging and prodrug release in response to HDAC. This design comprises a phenyl ester linker with tunable reactivity, facilitating efficient release of caged fluorophores/drugs upon deacetylation. We engineered a new fluorophore using a spirocyclic xanthene scaffold with ring-open property, affording NIRF/PA detection with high contrast. We showed that a nitro-substituted self-immolative linker allows sensitive NIRF/PA in vivo imaging of HDAC with minimal interference. A highly efficient prodrug system was further developed for targeted therapy in HDAC-overexpressed triple negative breast tumors in mice. Our study provides a valuable paradigm for HDAC-targeted NIRF/PA imaging and prodrug release in vivo, highlighting its potential for bioimaging and drug development.