Magnetoelectric core-shell CoFe2O4@BaTiO3 nanorods: their role in drug delivery and effect on multidrug resistance pump activity in vitro

Nanoparticle mediated targeted drug delivery has become a widespread area of cancer research to address premature drug delivery problems. We report the synthesis of magneto-electric (ME) core-shell cobalt ferrite-barium titanate nanorods (CFO@BTO NRs) to achieve on demand drug release in vitro. Physical characterizations confirmed the formation of pure CFO@BTO NRs with appropriate magnetic and ferroelectric response, favorable for an externally controlled drug delivery system. Functionalization of NRs with doxorubicin (DOX) and methotrexate (MTX) achieved up to 98% drug release in 20 minutes, under a 4 mT magnetic field (MF). We observed strong MF and dose dependent cytotoxic response in HepG2 and HT144 cells and 3D spheroid models (p < 0.05). Cytotoxicity was characterized by enhanced oxidative stress, causing p53 mediated cell cycle arrest, DNA damage and cellular apoptosis via downregulation of Bcl-2 expression. In addition, MF and dose dependent inhibition of Multidrug Resistance (MDR) pump activity was also observed (p < 0.05) indicating effectivity in chemo-resistant cancers. Hence, CFO@BTO NRs represent an efficient carrier system for controlled drug delivery in cancer nanotherapeutics, where higher drug uptake is a prerequisite for effective treatment.

Automated summary

In this study, the synthesis of magneto-electric core-shell nanorods was reported for targeted drug delivery. The results showed that the nanorods achieved up to 98% drug release under an external magnetic field, and exhibited strong magnetic field and dose dependent cytotoxic response in cells and 3D models. Additionally, the nanorods demonstrated the ability to inhibit the activity of multidrug resistance pumps, indicating effectiveness in chemo-resistant cancers. These findings suggest the potential importance of magneto-electric core-shell nanorods in cancer nanotherapeutics.