Advancing Colon Cancer Therapy with Folic Acid-Conjugated Gold/Magnetite Heterodimer Nanoparticles: Targeted Drug Delivery and Dual Thermo-Radiosensitization

Reducing therapeutic radiation doses, achieving localized hyperthermia, and ensuring precise chemotherapeutic release remain major challenges in multimodal cancer therapy. We developed folic acid–functionalized gold/magnetite heterodimer nanoparticles loaded with5-fluorouracil (5-FU@FA-Terp-HDNPs) to serve as targeted chemotherapeutic carriers, radiosensitizers, and mediators of alternating magnetic field (AMF)–induced hyperthermia. The nanoparticles were synthesized and extensively characterized, including assessment of hydrodynamic diameter, zeta potential, transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance ( 1 H-NMR), drug loading capacity, and in-vitro drug release profiles. The characterization confirmed the formation of spherical heterodimer nanoparticles with efficient 5-FU loading and controlled release, which was markedly accelerated under hyperthermic conditions. In vitro assays on HT29 colorectal cancer cells demonstrated enhanced cellular uptake and cytotoxicity relative to normal HUVEC cells, consistent with folate receptor overexpression. Combined chemo-thermo-radiotherapy (5-FU@FA-Terp-HDNPs + AMF at 43 °C + X-ray at 2 Gy) produced significantly greater apoptosis, reactive oxygen species (ROS) generation, and inhibition of cell proliferation compared to chemotherapy, hyperthermia, or radiotherapy alone (P < 0.0001). Folic acid–targeted 5-FU@FA-Terp-HDNPs function as multifunctional nanocarriers that enable precise drug delivery, radiosensitization, and localized hyperthermia. This integrated therapeutic platform enhances cancer-cell damage while reducing systemic toxicity, offering a promising strategy for advanced colorectal cancer treatment. • Multifunctional Folic acid–targeted 5-FU@Terp-HDNPs act as multifunctional nanocarriers. • Folic acid–targeted 5-FU@Terp-HDNPs act as radiosensitizers. • Folic acid–targeted 5-FU@Terp-HDNPs act as hyperthermia intensifiers. • Combined chemo-thermo-radiotherapy (5-FU@FA-Terp-HDNPs + AMF at 43 °C + X-ray by 2 Gy) induced markedly apoptosis. • Combined chemo-thermo-radiotherapy (5-FU@FA-Terp-HDNPs + AMF at 43 °C + X-ray by 2 Gy) induced reactive oxygen species (ROS) generation.