Hydrolysis-assisted synthesis of magnetic iron oxide-silica/poly(methacrylic acid) nanocomposites for pH- and thermo-responsive doxorubicin delivery

Abstract

Background

Cancer therapy faces challenges in targeted drug delivery, including poor bioavailability, limited tumor accumulation, and off-target toxicity. Nanomedicine offers a promising solution, utilizing nanoparticles to improve drug stability, enhance tumor targeting, and overcome these delivery limitations. This study aimed to develop nanocomposites composed of iron oxide nanoparticles (IONPs), silica (SiO₂), and poly(methacrylic acid) (PMAA) for targeted delivery of an anticancer drug, doxorubicin (DOX). The combination of these materials was intended to improve the efficiency and specificity of drug delivery in cancer therapy.

Methods

The IONPs were synthesized through a co-precipitation method and coated with SiO₂ using the Stöber process, with vinyl-functionalized silane serving as a coupling agent. The IONPs@SiO₂@PMMA nanocomposites were then fabricated by emulsion polymerization of PMAA, and IONPs@PMAA nanocomposites were synthesized via hydrolysis. DOX was successfully loaded into the nanocomposites. The characterization of the nanocomposites was performed using high-resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Cytotoxicity was assessed, and the drug loading capacity and release behavior were analyzed using UV–visible spectroscopy.

Significant Findings

The nanocomposites exhibited negligible cytotoxicity. UV–Vis analysis revealed that increasing the concentrations of polymer and DOX enhanced the drug loading capacity, achieving a maximum of 91.2%. Drug release studies demonstrated that DOX release was sensitive to both temperature and pH, with the highest release observed at 42 °C and pH 5.4. The release rate increased by 20–35%, reaching a peak of 86.7%. Additionally, the drug loading efficiency improved with increasing PMAA contents. Kinetic analysis showed that the release of DOX followed the Korsmeyer-Peppas model, indicating Fickian diffusion as the primary release mechanism. The diffusivity of DOX was calculated to be 1.7 × 10^–20 m²/s using the Crank's diffusion model. This study demonstrates a promising approach for enhancing the targeted delivery and controlled release of DOX, potentially improving cancer treatment outcomes by addressing key challenges in drug delivery.