Tumor-targeted metabolic inhibitor prodrug labelled with cyanine dyes enhances immunoprevention of lung cancer  

作　　者：Wen Li Jiali Huang Chen Shen Weiye Jiang Xi Yang Jingxuan Huang Yueqing Gu Zhiyu Li Yi Ma Jinlei Bian 

机构地区：[1]State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China [2]Department of Biomedical Engineering,School of Engineering,China Pharmaceutical University,Nanjing 210009,China [3]Jiangsu Key Laboratory of Drug Design and Optimization,Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第2期751-764,共14页药学学报（英文版）

基　　金：support from the National Natural Science Foundation of China(82072058,91859204,82073702);Natural Science Foundation of Jiangsu Province for Excellent Young Scientists(Grant BK20211580,China);Qinglan Project of Jiangsu Province of China.“Double First-Class”university project(CPUQNJC2205,China).

摘　　要：Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs.To address this challenge,we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug,specifically 6-diazo-5-oxo-L-norleucine(DON),using a thioketal linkage(TK).This system enables imaging,chemotherapy,photodynamic therapy,and on-demand drug release upon radiation exposure.The optimized prodrug,DON-TK-BM3,incorporating cyanine dyes as the fluorophore,displayed potent reactive oxygen species release and efficient tumor cell killing.Unlike the parent drug DON,DON-TK-BM3 exhibited no toxicity toward normal cells.Moreover,DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects,including gastrointestinal toxicity,in mice.This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

关 键 词：Smart prodrug system Glutamineantagonists IMMUNOTHERAPY PHOTODYNAMICTHERAPY Reactive oxygen species Metabolicinhibitor Cyaninedye Non-small-cell lung cancer(NSCLC) 

分 类 号：R943[医药卫生—药剂学]