A Spatiotemporally Controlled Gene‐Regulation Strategy for Combined Tumor Therapy Based on Upconversion Hybrid Nanosystem

作者：Fang Wang, Zechao Liu, Yuechen Liu, Jiayi Zhang, Weizhe Xu, Bei Liu, Zhaogang Sun, Hongqian Chu · 发表于：Advanced Science · 年份：2024 · DOI：10.1002/advs.202405640 · 被引用次数：13 · 研究领域：Nanoplatforms for cancer theranostics、Photoreceptor and optogenetics research、Photochromic and Fluorescence Chemistry

The lack of precise spatiotemporal gene modulation and therapy impedes progress in medical applications. Herein, a 980 nm near-infrared (NIR) light-controlled nanoplatform, namely URMT, is developed, which can allow spatiotemporally controlled photodynamic therapy and trigger the enzyme-activated gene expression regulation in tumors. URMT is constructed by engineering an enzyme-activatable antisense oligonucleotide, which combined with an upconversion nanoparticle (UCNP)-based photodynamic nanosystem, followed by the surface functionalization of triphenylphosphine (TPP), a mitochondria-targeting ligand. URMT allows for the 980 nm NIR light-activated generation of reactive oxygen species, which can induce the translocation of a DNA repair enzyme (namely apurinic/apyrimidinic endonuclease 1, APE1) from the nucleus to mitochondria. APE1 can recognize the basic apurinic/apyrimidinic (AP) sites in DNA double-strands and perform cleavage, thereby releasing the functional single-strands for gene regulation. Overall, an augmented antitumor effect is observed due to NIR light-controlled mitochondrial damage and enzyme-activated gene regulation. Altogether, the approach reported in this study offers high spatiotemporal precision and shows the potential to achieve precise and specific gene regulation for targeted tumor treatment.