Apoferritin-Cu(II) Nanoparticles Induce Oncosis in Multidrug-Resistant Colon Cancer Cells.

Multidrug resistance (MDR) limits the application of clinical chemotherapeutic drugs. There is an urgent need to develop non-apoptosis-inducing agents that circumvent drug resistance. Herein, four therapeutic copper complexes encapsulated in natural nanocarrier apoferritin (AFt-Cu1-4) are reported. Although they are isomers, they exhibited significantly different organelle distributions and cell death mechanisms. AFt-Cu1 and AFt-Cu3 accumulated in the cytoplasm and induced autophagy, whereas AFt-Cu2 and AFt-Cu4 could quickly enter the nucleus and trigger oncosis. Excitedly, AFt-Cu2 and AFt-Cu4 showed a strong tumor growth inhibition effect in mice models bearing multidrug-resistant colon xenograft via intravenous injection. To the best of our knowledge, this is the first example of metal-based nucleus-targeted oncosis inducers overcoming multidrug resistance in vivo. This article is protected by copyright. All rights reserved.