Multifunctional Fe₃O₄ mesocrystals for cancer therapy: integrating hyperthermia and targeted drug delivery

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, additive-free solvothermal synthesis of Fe₃O₄ mesocrystals (∼205 nm) and investigate their morphological evolution by correlating the structural changes with respect to magnetic properties. The Fe₃O₄ mesocrystals exhibit a high saturation magnetization of 87 emu g^-1, surpassing that of conventional nanoparticles (55.29 emu g^-1) suitable for magnetic hyperthermia. A therapeutic temperature of 42 °C was reached at 5 and 10 mg mL^-1 under applied fields of 20 and 26.7 kA m^-1 in water and 2% agar media within the clinical safety limit. Furthermore, they exhibit an excellent drug encapsulation efficiency of 41.09% for paclitaxel (PTX) drugs, significantly outperforming that of the nanoparticles (19.4%), which is attributed to the internal voids of mesocrystals, nanoparticle building units and hierarchical structures with release profiles of 28% and 41% at pH 7.4 and 5.5, respectively. <i>In vitro</i> studies reveal 82% biocompatibility with L-929 fibroblast cells and 60% cell viability against HCT 116 colon cancer cells at 1 mg mL^-1. At this concentration, Fe₃O₄ mesocrystals embedded with PTX show a 95% reduction in cancer cell viability. We also probed the structural characteristics using XRD, Raman, FT-IR, SEM, TEM and XPS analyses. 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.