Harnessing the Chemo-photothermal Effects of Magneto-polymeric Nanohybrids for Near-Infrared (NIR) Responsive Delivery of Doxorubicin in Cancer Cells

Photothermal therapy is currently the most discussed noninvasive therapy for eradicating cancer cells due to its ability to penetrate deeper tissues. A number of NIR-responsive nanomaterials have been effectively used along with anticancer drugs that can potentially exhibit combined chemo-photothermal effects, which can provide multistrategy approaches toward cancer management. This research mainly focused on the ultrasonic atomization-led synthesis of NIR-responsive nanohybrids with chitosan and gold-coated iron oxide nanoparticles loaded with doxorubicin (DOX) (CGMD nanohybrids), and the study of their chemo-photothermal application toward the eradication of cancer. The functional and morphological characterization of the CGMD nanohybrids was performed using various techniques, including absorption spectroscopy, Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), Dynamic Light Scattering (DLS), and ζ-potential measurements. The synthesized nanohybrids were monodisperse, with a mean particle size of 118 ± 13 nm, incorporating gold-coated iron oxide nanoparticles of 27 ± 9 nm. The encapsulation of DOX in the nanohybrids was found to be 82.37 ± 7%, and released approximately 51% of DOX over a period of ∼7 days, demonstrating a sustained and controlled release profile. The photothermal efficacy was determined with NIR laser exposure (808 nm, 0.6W) for 10 min, which resulted in a 24.9 °C rise in the temperature. The CGMD nanohybrids exhibited 7× faster DOX release with multiple NIR stimulations. Several <i>in vitro</i> studies have been performed with CGMD nanohybrids on MCF-7 breast cancer cells. Without laser exposure, the CGMD nanohybrids exhibited cytotoxic effects on MCF-7 breast cancer cells with an IC₅₀ of 1.05 μg/mL after 48 h of incubation. In contrast, upon laser exposure, an improved cytotoxic effect was observed in just 12 h. The results were then translated to a 3D spheroid model generated from MCF-7 cells. Overall, the CGMD nanohybrids demonstrated enhanced efficacy in inhibiting cancer cell proliferation in both 2D and 3D cell models using dual chemo-photothermal therapy.