Magnetic Nanocarriers Enhance Drug Delivery Selectively to Human Leukemic Cells

Abstract

Selective drug delivery to human leukemia cells using a nanoparticulate chemotherapeutic formulation is hugely needed. In this work, we report the development of a magnetic nanocarrier made of PVP-stabilized magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising selective drug carrier to different types of human leukemia and normal cells. Our results revealed that while the unloaded MNPs were not potent to any of the cells, Dox@PMNPs showed significant toxicities, effectively killing the different leukemia cells, albeit at different inhibitory concentrations. Interestingly and superior to free Dox, Dox@PMNPs showed enhanced and significant inhibition towards the human monocytic THP-1 cells compared to human promyelocytic leukemia cells HL-60 (2-fold enhanced cytotoxicities), with the least potency towards the normal peripheral blood mononuclear cell (PBMC) cells (up to 6-fold). Nonetheless, free Dox was found to be concurrently less toxic to all the three cell lines tested. The cytotoxic effects obtained were further confirmed by live confocal imaging and electron microscopy. Both imaging techniques confirmed distinct morphological changes (membrane blebbing, shrinkage, and condensation) corresponding to typical apoptotic features in the treated leukemia cells compared to normal PBMC cells. The observed enhanced cytotoxic effects of Dox@PMNPs is mostly dependent upon the selective and differential endocytic uptake of Dox@PMNPs, with subsequent release of Dox intracellularly to the cytoplasm after 6 h, which then translocates to the nucleus after 24 h, causing apoptotic cell death. Importantly, magnetic Dox nanocarrier described here reduces the unwanted diffusive side effects of the free drug and allows selective drug delivery to leukemic cells, allowing its potential use for leukemic patients’ theranostics.