Autophagy-Dependent Apoptosis Induced by Apoferritin–Cu(II) Nanoparticles in Multidrug-Resistant Colon Cancer Cells
Kai Xiong, Ying Zhou, Johannes Karges, Ke‐Jie Du, Jinchao Shen, Ming‐Wei Lin, Fangmian Wei, Jun‐Feng Kou, Yu Chen, Liang‐Nian Ji, Hui Chao
Abstract
Chemotherapy continues to be the most commonly applied strategy for cancer. Despite the impressive clinical success obtained with several drugs, increasing numbers of (multi)drug-resistant tumors are reported. To overcome this shortcoming, novel drug candidates and delivery systems are urgently needed. Herein, a therapeutic copper polypyridine complex encapsulated in natural nanocarrier apoferritin is reported. The generated nanoparticles showed higher cytotoxicity toward various (drug-resistant) cancer cell lines than noncancerous cells. The study of the mechanism revealed that the compound triggers cell autophagy-dependent apoptosis. Promisingly, upon injection of the nanodrug conjugate into the bloodstream of a mouse model bearing a multidrug-resistant colon tumor, a strong tumor growth inhibition effect was observed. To date, this is the first study describing the encapsulation of a copper complex in apoferritin that acts by autophagy-dependent apoptosis.