A Dual-Stimuli Responsive Nanoplatform via Atomic Layer Deposition of Gold on CoFe2O4 for Thermally Gated Doxorubicin Delivery in Colorectal Cancer

Yutian Zhang,1,* Lang Liu,2,* Tianlin Wang,3 Ziyi Qu,4 Lei Liang,1 Huizhen Li,3 Hong Wang5 1Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 300100, People’s Republic of China; 2College of Meteorology and Oceanography, National University of Defense Technology, Changsha, Hunan, 410073, People’s Republic of China; 3Department of Gastroenterology, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300100, People’s Republic of China; 4Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People’s Republic of China; 5Department of General Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huizhen Li, Email [email protected] Hong Wang, Email [email protected]: Targeted chemotherapy for colorectal cancer is often limited by nonspecific drug distribution and systemic toxicity. To improve local therapeutic efficacy and reduce side effects, we designed a thermally gated, dual-stimuli-responsive nanoplatform for controlled doxorubicin (DOX) delivery.Methods: CoFe2O4 (CFO) nanocubes were synthesized and coated with Au nanoparticles via atomic layer deposition (ALD) to obtain CFO/Au nanocomposites with enhanced photothermal properties while retaining magnetic responsiveness. The optimal sample (CFO/Au-2) was further modified with poly(acrylic acid) (PAA) to improve aqueous dispersibility and provide abundant carboxyl groups for DOX loading, yielding CFO/Au-2/PAA/DOX. A thermal gate was then constructed using 1-tetradecanol (TD), a phase-change material with a melting point of ~38 °C, to obtain CFO/Au-2/PAA/DOX/TD. The structural, magnetic, and photothermal properties, DOX loading and release behavior, and in vitro cytotoxicity against SW620 colorectal cancer cells were systematically evaluated under near-infrared (NIR) irradiation and/or alternating magnetic field (AMF).Results: CFO/Au-2/PAA/DOX/TD exhibited a high DOX loading capacity (~26 wt%) and good colloidal stability. Minimal DOX leakage occurred at physiological temperature, confirming effective encapsulation by solid TD. Under NIR and/or AMF stimulation, the nanocomposite generated pronounced local heating, induced TD melting, and triggered rapid DOX release, with the combined NIR + AMF condition producing the fastest release profile. In vitro, the carrier without DOX showed minimal cytotoxicity toward SW620 cells, whereas CFO/Au-2/PAA/DOX/TD under dual stimulation produced significantly enhanced cytotoxicity toward SW620 cells compared with free DOX at the same drug concentration.Conclusion: This ALD-engineered CFO/Au-2/PAA/DOX/TD nanoplatform integrates magnetic and photothermal heating with thermally gated, dual-stimuli-responsive drug release, enabling precise spatiotemporal control of DOX delivery. The results suggest strong potential for combined and localized colorectal cancer therapy with reduced systemic toxicity.Keywords: colorectal cancer, CoFe2O4 nanocubes, atomic layer deposition, doxorubicin delivery, photothermal therapy, phase-change material