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

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外文摘要：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 ther-apy,and on-demand drug release upon radiation exposure.The optimized prodrug,DON-TK-BM3,incor-porating 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.

外文关键词：

Smart prodrug systemGlutamine antagonistsImmunotherapyPhotodynamic therapyReactive oxygen speciesMetabolic inhibitorCyanine dyeNon-small-cell lung cancer(NSCLC)

作者：

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

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作者单位：

State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China

Department of Biomedical Engineering,School of Engineering,China Pharmaceutical University,Nanjing 210009,China

Jiangsu Key Laboratory of Drug Design and Optimization,Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China

基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNatural Science Foundation of Jiangsu Province for Excellent Young Scientists,ChinaQinglan Project of Jiangsu Province of China."Double First-Class"university project,China

项目编号：

820720589185920482073702BK20211580CPUQNJC22 05

出版年：

2024

DOI：

10.1016/j.apsb.2023.10.020

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(2)

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