Dual pH- and magnetic field-sensitive magnetic κ-carrageenan-graft-poly(2-hydroxypropyl methacrylamide)/iron oxide nanoparticles synthesized by microwave-assisted method for doxorubicin delivery

Abstract

Magnetic nanomaterials have played a critical role and attracted significant interest in biomedical fields, including magnetic hyperthermia and targeted drug delivery. In this study, we designed and synthesized magnetic κ-carrageenan-graft-poly (2-hydroxypropyl methacrylamide) (CR-g-PHMA) coated iron oxide (Fe₃O₄) nanoparticles (CR-g-PHMA/Fe₃O₄ NPs) for the magnetic field- and pH-triggered release of the antineoplastic drug doxorubicin (Dox) in cancer therapy. To achieve this, 2-hydroxypropyl methacrylamide was initially grafted onto κ-carrageenan, and afterward, the CR-g-PHMA copolymer was functionalized with Fe₃O₄ NPs using a microwave-assisted co-precipitation method. The Fe₃O₄ and CR-g-PHMA components perform as a superparamagnetic core and a pH-sensitive shell, respectively. The magnetic properties, surface morphology, structure, size, and stability of the synthesized CR-g-PHMA/Fe₃O₄ magnetic NPs were characterized using VSM, TEM, FTIR, XRD, UV, and DLS methods. The in vitro release of Dox from the CR-g-PHMA/Fe₃O₄ NPs demonstrated good magnetic field- and pH-sensitive behavior. Under a 100 kHz AMF, Dox release was significantly accelerated, reaching 100 % within 5 h under acidic conditions. Furthermore, the impact of grafting yield and Fe₃O₄ percentage on Dox release showed an enhanced release rate. The in vitro cytotoxicity assessment confirmed that CR-g-PHMA/Fe₃O₄ NPs exhibited good biocompatibility against both A549 carcinoma and L929 normal fibroblast cells. In addition, the CR-g-PHMA/Fe₃O₄/Dox NPs demonstrated a significantly improved cytotoxicity towards A549 cells compared to free Dox. These findings indicate that the dual magnetic field- and pH-responsive CR-g-PHMA/Fe₃O₄/Dox NPs have potential for effective and controlled cancer therapy applications.