Multifunctional Fe3O4 Mesocrystals for Cancer Therapy: Integrating Hyperthermia and Targeted Drug Delivery

Abstract

Mesocrystals with hierarchical architecture and crystallographically aligned nanoparticles hold immense potential for advanced applications in catalysis, energy storage and biomedicine. However, challenges arise for biomedical applications due to their surfactant-controlled growth, lack of understanding of magnetic mesocrystals and their dopant effect. Herein, we report a facile, and additive-free solvothermal synthesis of Fe₃O₄ mesocrystals (~205 nm) and investigated their morphological evolution by correlating the structural changes with respect to magnetic properties. The Fe₃O₄ mesocrystals exhibit high saturation magnetization of 87 emu/g surpassing conventional nanoparticles (55.29 emu/g) suitable for magnetic hyperthermia. The therapeutic temperature of 42°C was reached in 5 and 10 mg/mL under applied fields of 20 and 26.7 kA/m both in water and 2% agar media within the clinical safety limit. Furthermore, they exhibit excellent drug encapsulation efficiency of 41.09% for paclitaxel drugs significantly outperforming the nanoparticles (19.4%), attributed to mesocrystals internal voids, nanoparticle building units and hierarchical structure with release profile of 28% and 41% at pH 7.4 and 5.5 respectively. In vitro studies reveal 82% biocompatibility with L-929 fibroblast cells and 60% cytotoxicity against HCT 116 colon cancer cells at 1 mg/mL. At this concertation, Fe₃O₄ mesocrystals embedded with PTX shows 95% reduction in cancer cell viability. We also probed the structural characteristics using XRD, Raman, FT-IR, SEM, TEM and XPS analysis. By integrating magnetic hyperthermia with pH-dependent drug release, this work establishes Fe₃O₄ mesocrystals as a dual-functional platform for targeted cancer therapy, offering a transformative approach to overcome the limitations in nanomedicine.