Tailoring nanoparticles design for enhanced heating efficiency and improved magneto-chemo therapy for glioblastoma

Development of multifunctional magnetic nanomaterials (MNPs) with improved heat-generating capabilities and effective combination with localized chemotherapy has emerged as a promising therapeutic regime for solid tumors like glioblastoma. In this regard, the shape-dependent hyperthermic and chemo-therapeutic potential of nanomaterials, has not been extensively explored. Here we present, development of various morphological designs of MNPs including spherical, clusters, rods and cubic; to compare the effect of shape on tuning the properties of MNPs that are relevant to many potential biomedical applications like drug delivery, cellular uptake and heat generation. The study includes extensive comparison of morpho-structural characteristics, size distributions, chemical composition, surface area measurements and magnetic properties of the variable shaped MNPs. Further the heating efficiencies in aqueous and cellular environments and heat triggered drug release profiles for successful magneto-chemotherapy were compared among all in-house synthesized MNPs. Under biosafety limit considerations given by Hergt's limit (H*f value <5 × 10⁹ Am^-1 s^-1), cuboidal shaped MNPs demonstrated highest heating efficiency owing to magnetosome-like chain formation along with sustained drug release profile as compared to other synthesized MNPs. The mechanism of cancer cell death mediated via magneto-chemotherapy was elucidated to be the oxidative stress-mediated apoptotic cell death pathway. In vivo studies further demonstrated complete tumor regression only in the magneto-chemotherapy treated group. These findings suggest the potential of combinatorial therapy to overcome the clinical limitations of the independent therapies for advanced thermotherapy of glioblastoma.