Flame-made nanoparticles for oral delivery in magnetic hyperthermia and MRI for colorectal cancer theranostics

Magnetic hyperthermia therapy­ induced with superparamagnetic iron oxide nanoparticles (SPIONs) is a promising alternative for the treatment of chemo- and radiotherapy resistant-cancers. However, SPIONs in clinical use for magnetic hyperthermia rely on injecting high doses directly to the tumor. Oral delivery of SPIONs to locally treat gastrointestinal cancers has not been widely explored. In this study, we developed a physically stable methoxy polyethylene glycol (mPEG) functionalized SPION (mPEG-Mn_0.6Zn_0.4Fe₂O₄) intended for oral delivery. By combining localized magnetic hyperthermia treatment and magnetic resonance imaging (MRI), these nanoparticles could be used as a theranostic agent against colorectal cancer (CRC). CRC cell lines SW480 and Caco-2 were used to evaluate particle cytotoxicity, uptake, and magnetic hyperthermia outcomes. To gain a comprehensive understanding of the therapeutic effect of the SPIONs, <i>in vitro</i> cell studies were conducted in both inverted and upright cell configurations. The mPEG-Mn_0.6Zn_0.4Fe₂O₄nanoparticles exhibited excellent and consistent heating performance in biosimilar colonic environments, with a more than 5°C increase within 10 min under an alternating magnetic field (AMF). The <i>r2</i> relaxivity of the mPEG-Mn_0.6Zn_0.4Fe₂O₄was stronger than that of the g-Fe₂O₃ nanoparticles rendering the formera better T2 MRI contrast agent. Magnetic hyperthermia in CRC cells showed a significant cell death in the upright configuration compared to the inverted one. This could be attributed to a higher extent of direct nanoparticle-cell contact in the former caused by nanoparticle sedimentation onto the cell surface. Overall, the magnetic hyperthermia outcomes were found sensitive to experimental parameters such as cell lines, cell configurations, and AMF exposure times and should be systematically considered during preclinical development of SPIONs for new biomedical applications.