Malic acid grafted Fe3O4 nanoparticles for controlled drug delivery and efficient heating source for hyperthermia therapy

Tailoring surface features is essential for creating specific functional properties on superparamagnetic Fe3O4 nanoparticles for biomedical applications. In this regard, we explored the use of malic acid as a surface passivating agent for designing biocompatible, highly water-dispersible Fe3O4 magnetic nanocarriers (MMNCs) for high payload of anticancer drug, doxorubicin hydrochloride (DOX). The efficacious grafting of malic acid onto the surface of Fe3O4 was apparent from infrared spectroscopy, dynamic light scattering, zeta-potential and thermogravimetric measurements. XRD and TEM analyses revealed the formation of highly crystalline single-phase Fe3O4 nanoparticles. They showed good aqueous colloidal stability, pH de-pendent surface charge characteristics and superparamagnetic behavior at room temperature. The electrostatic conjugation of drug onto the surface of MMNCs was optimized by varying the ratio of DOX to MMNCs, and a maximum loading efficiency of 72% was achieved at their 1:10 ratio. The DOX conjugated MMNCs (DOX-MMNCs) exhibited pH dependent controlled release characteristics. These DOX-MMNCs demonstrated dose dependent cellular uptake and retained considerable toxicity of DOX towards breast cancer (MCF-7) cell line. Further, our magnetic hyperthermia studies showed excellent heating efficiency of these MMNCs within the permissible limit of field strength and frequency reported for a safe application of hyperthermia to patients. Specifically, a water-dispersible surface decorated magnetic formulation was developed for pH-responsive controlled release of chemotherapeutic drug and efficient heating source for hyperthermia therapy. (C) 2021 Elsevier B.V. All rights reserved.