Nanodrugs Detonate Lysosome Bombs

Frontiers in Pharmacology

Jia Huang³  Xiaoyuan Wang³  Chong Liu⁴  Yuqi Yang⁵  Min Liu⁵  Yunrong Yang⁵  Qiong Huang⁵  Jinping Zhang⁵  Xingyu Long⁶  Qiaohui Chen⁶  Niansheng Li⁶  Yuting Xiang⁶  Zuoxiu Xiao⁶ 

[1] Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China;Departments of Clinical Pharmacology and Pharmacy, Hunan Key Laboratory of Pharmacogenetics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China;Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China;Institute of Clinical Pharmacology, Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Central South University, Changsha, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China;Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China;

关键词: lysosomal membrane permeabilization;    nanomaterials;    nanodrugs;    cancer treatment;    chemodynamic therapy;    magnetic nanoparticles;   

DOI  :  10.3389/fphar.2022.909504

来源: DOAJ

【 摘 要 】

Cancer cell lysosomes contain various hydrolases and non-degraded substrates that are corrosive enough to destroy cancer cells. However, many traditional small molecule drugs targeting lysosomes have strong side effects because they cannot effectively differentiate between normal and cancer cells. Most lysosome-based research has focused on inducing mild lysosomal membrane permeabilization (LMP) to release anticancer drugs from lysosomal traps into the cancer cell cytoplasm. In fact, lysosomes are particularly powerful “bombs”. Achieving cancer cell-selective LMP induction may yield high-efficiency anticancer effects and extremely low side effects. Nanodrugs have diverse and combinable properties and can be specifically designed to selectively induce LMP in cancer cells by taking advantage of the differences between cancer cells and normal cells. Although nanodrugs-induced LMP has made great progress recently, related reviews remain rare. Herein, we first comprehensively summarize the advances in nanodrugs-induced LMP. Next, we describe the different nanodrugs-induced LMP strategies, namely nanoparticles aggregation-induced LMP, chemodynamic therapy (CDT)-induced LMP, and magnetic field-induced LMP. Finally, we analyze the prospect of nanodrugs-induced LMP and the challenges to overcome. We believe this review provides a unique perspective and inspiration for designing lysosome-targeting drugs.

【 授权许可】

Unknown