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

• Published in: Journal of magnetism and magnetic materials Vol. 448; pp. 199 - 207
• Main Authors: Adimoolam, Mahesh G., Amreddy, Narsireddy, Nalam, Madhusudana Rao, Sunkara, Manorama V.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.02.2018
• ISSN: 0304-8853
• DOI: 10.1016/j.jmmm.2017.09.018

•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.