Autophagy-Dependent Apoptosis Induced by Apoferritin–Cu(II) Nanoparticles in Multidrug-Resistant Colon Cancer Cells

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.