In vitro evaluation of bortezomib-loaded superparamagnetic iron oxide nanoparticles for multiple myeloma cells under guide-targeted variable magnetic fields

Official URL: https://dx.doi.org/10.1002/cnma.202500225

Multiple myeloma (MM) is a type of hematological cancer. Bortezomib is an effective proteasome inhibitor used in its treatment. However, Bortezomib causes many side effects such as peripheral neuropathy and thrombocytopenia, which affect the quality of life in patients. Prolonged use of Bortezomib can lead to drug resistance in MM patients. Superparamagnetic iron oxide nanoparticles (SPIONs) are oxide nanoparticles that exhibit the phenomenon of superparamagnetism. When an external magnetic field is applied, they become magnetized to saturation levels, but they do not show any magnetic interaction upon its removal. In this study, a drug delivery system is proposed that can precisely target cancer cells, persist in circulation, exhibit cytotoxic effects even at lower concentrations, and minimize side effects. For this, Bortezomib is successfully loaded into SPIONs. Controlled drug release is achieved solely in the acidic environment of the vacuoles. This approach results in higher growth inhibition compared to the equivalent dose (2.5 nM) of free Bortezomib in RPMI 8226 cells. The magnetic drive system that has been developed generates irregular magnetic fields with variable fluxes ranging from 2 to 60 mT on the rotary table. Moreover, the use of the developed variable magnetic field device significantly enhances the growth-inhibitory effect on the cells, with Bim/Mcl-1 shifts consistent with an apoptosis-associated response. Targeted therapy at lower doses becomes possible by using the synthesized Bortezomib-loaded SPION (2.5 nM–10 µg) in combination with a magnetic field device. The findings of this study not only reveal an effective drug delivery system for MM cells but also hold promise for potential treatment and clinical applications for other cancer types.