Magnetic Nanoparticle-Mediated Multimodal Cancer Therapy: Hyperthermia, Controlled Drug Release, and Antibody-Based Precision

Abstract

Research in cancer therapies is rapidly advancing and demands the exploration of innovative approaches to further improve the efficacy of treatment. Here a multimodal approach for cancer therapy is reported which combines bioactive targeting, magnetic hyperthermia, and controlled drug release. For this, a nanoformulation MNP-Chi-Dox-Ab, is bioengineered by conjugating CA 15-3 antibodies to doxorubicin-loaded functionalized magnetic nanoparticles (MNPs). Solvothermally synthesized MNPs of uniform spherical shape and size are functionalized with thermo-pH-responsive chitosan. The nanoformulation showed higher drug release of ≈65% at pH 5 and 42 °C temperature compared to the release at physiological pH and temperature. Furthermore, in an alternating magnetic field drug release is enhanced to 74%. Cytotoxicity studies in MCF-7 breast cancer cells confirm the active targeting potential of the nanoformulation. For the nanoformulation without bioactive molecule (anti-CA 15-3) only 18% cancer cell death is noted whereas with the conjugation of anti-CA 15-3, 43% cell death is recorded. Flow cytometry studies revealed an increased apoptotic population at hyperthermic temperature (42 °C) compared to the physiological temperature. These results suggest that MNP-Chi-Dox-Ab nanoformulation represents a promising multimodal platform for synergistic breast cancer therapy by combining active targeting, controlled drug release, and hyperthermia.