Autophagy-Dependent Apoptosis Induced by Apoferritin-Cu(II) Nanoparticles in Multidrug-Resistant Colon Cancer Cells.
Kai XiongYing ZhouJohannes KargesKejie DuJinchao ShenMingwei LinFangmian WeiJunfeng KouYu ChenLiangnian JiHui ChaoPublished in: ACS applied materials & interfaces (2021)
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.
Keyphrases
- drug resistant
- multidrug resistant
- endoplasmic reticulum stress
- cell cycle arrest
- cell death
- acinetobacter baumannii
- gram negative
- induced apoptosis
- oxidative stress
- klebsiella pneumoniae
- papillary thyroid
- signaling pathway
- mouse model
- single cell
- mesenchymal stem cells
- lymph node metastasis
- stem cells
- pi k akt
- cancer therapy
- bone marrow
- cell proliferation