Gelatin grafted magnetic hydroxyapatite nanocomposite for chemo-hyperthermia therapy

Abstract

The combinatorial therapy comprising chemotherapy and magnetic hyperthermia could provide a promising treatment modality for cancer by making the treatment safer and more effective. In the present study, we have developed magnetic-hydroxyapatite nanocomposite with an aim to be used for chemo-hyperthermia therapy. A soft-chemical approach was employed for the synthesis of nanocomposite, where phosphate coated Fe₃O₄ nanoparticles were used as a core and hydroxyapatite was anchored on their surface through chemical precipitation. The nanocomposite was in-situ functionalized with gelatin moieties for providing aqueous colloidal stability as well as active sites for the binding of drugs. The nanocomposite showed high payload of anticancer drug, doxorubicin hydrochloride (DOX) with a drug content of ∼ 8.2 %. A pH-responsive sustained release of drug was observed with pronounced release under acidic pH conditions, which is favourable for cancer therapy. The cytotoxicity assay in human cancer cells (MCF-7 and A549) suggested non-toxic behaviour of nanocomposite, while DOX loaded nanocomposite showed enhanced toxicity with higher cellular uptake in cancer cells as compared to free DOX. The nanocomposite exhibited superparamagnetic behaviour with magnetic field strength and particle concentration dependent heating efficacy under AC magnetic field (AMF). The specific absorption rate values of nanocomposite were in the appropriate range (100 – 300 W/g under AMF of 0.422 kOe) required for magnetic hyperthermia treatment. Overall, the study demonstrates that the developed nanocomposite could simultaneously serve as a drug carrier and heating source for hyperthermia therapy.