A simple approach to design chitosan functionalized Fe3O4 nanoparticles for pH responsive delivery of doxorubicin for cancer therapy

Highlights: • Simple process for the synthesis of easily redispersible chitosan stabilised SPIONs. • Imine functionality on the SPION facilitates drug release at the pH of the tumor micro environment. • The Fe₃O₄-Dox conjugates showed improved therapeutic efficiency compared to free Dox. • Along with improved cancer therapy the conjugates also exhibit reduced toxicity to normal cells. The use of magnetic nanoparticles (MNPs) in cancer therapy offer many advantages due to their unique size, physical and biocompatible properties. In this study we have developed a formulation, comprising of anti-cancer drug doxorubicin (Dox) conjugated to iron oxide nanoparticles via a pH sensitive imine linker. Different amounts of chitosan functionalized superparamagnetic iron oxide nanoparticles (Fe₃O₄-CHI) were synthesized in-situ by a simple hydrolysis method at room temperature. The synthesized nanoparticles were well characterized by TEM, Zeta Potential, TOC, XPS, TGA and VSM for their physicochemical properties. Dox was conjugated to the Fe₃O₄-CHI nanoparticles via a glutaraldehyde cross linker with the imine (CN) bond, which is sensitive to cleavage in the pH range of 4.4–6.4. The synthesized Fe₃O₄-Dox nanoparticles exhibited enhanced drug release in lower pH conditions which mimics the tumor microenvironment or intracellular organelles such as endosomes/lysosomes. The cell uptake and therapeutic efficacy of Fe₃O₄-Dox nanoparticles carried out in ovarian cancer cell (SK-OV-3) and breast cancer cell line (MCF7) showed improved therapeutic efficacy of Dox by nearly four-fold with Fe₃O₄-Dox nanoparticles.