Conjugation of hydrazine to PEGylated silica-coated magnetite nanoparticles as pH-responsive magnetic nanocarriers for covalent loading and controlled release of doxorubicin

Breast cancer is a major health issue among women, and doxorubicin (DOX) is a commonly used treatment. However, its clinical application is limited by its considerable toxicity. This study introduces an acidity-responsive magnetite nanoparticle-based nanocarrier for effective breast cancer treatment. The magnetite nanoparticles were initially coated with [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane, an epoxysilane cross-linker, to enhance their stability and functional properties. Subsequently, NH2-PEG-COOH was conjugated to epoxy-functionalized silica-coated magnetite nanoparticles to improve biocompatibility and introduce reactive carboxyl groups. These carboxyl groups were further modified with hydrazine via carbodiimide-mediated amidation to construct magnetic nanocarriers (MNC). DOX was loaded into the system via acid-sensitive hydrazone bonds, resulting in the final MNC-DOX formulation. The DOX loading process followed the Ho-McKay model, demonstrating chemical adsorption kinetics with a high loading capacity of 433.147 mg/g. The acid-sensitive hydrazone bond facilitated rapid DOX release in response to the acidic tumor microenvironment, with release kinetics following the Korsmeyer-Peppas model, indicative of Fickian diffusion. In vitro cytotoxicity assays revealed that MNC-DOX exhibited significant cytotoxicity against MCF-7 breast cancer cells. This novel MNC-DOX formulation holds great potential for enhancing cancer therapy, highlighting its responsiveness to subtle pH changes and its ability to improve the targeted delivery and controlled release of chemotherapeutic agents.