pH-Labile Magnetic Nanocarriers for Intracellular Drug Delivery to Tumor Cells

We report the development of pH-labile ascorbic acid-coated magnetic nanocarriers (AMNCs) for effective delivery of the anticancer drug doxorubicin hydrochloride (DOX) to tumor cells. The uniqueness of this drug delivery system lies in the covalent conjugation of DOX through carbamate and hydrazone bonds, resulting in a slow and sustained drug release profile at different environmental acidities. X-ray diffraction and transmission electron microscopy analyses reveal the formation of crystalline single-phase Fe₃O₄ nanoparticles with an average size of 10 nm. The changes in the interfacial characteristics of the nanocarriers and the presence of organic coatings are probed by infrared spectroscopy, dynamic light scattering, zeta potential, and thermogravimetric measurements. AMNCs show high colloidal stability in aqueous and cell culture media and possess good magnetic field responsivity and protein resistance characteristics. The drug-loaded nanocarriers exhibited sustained pH-triggered release of drug molecules in acidic mediums, substantial cellular internalization, and significant toxicity toward the proliferation of mouse skin fibrosarcoma (WEHI-164), human breast cancer (MCF-7), and human lung cancer (A549) cells. However, it showed significantly lower toxicity in human normal lung (WI26VA) cells. Overall, these results suggest a pH-sensitive drug release of nanoformulations, which showed selective toxicity to tumor than normal cells.