Development and optimization of a new hybrid chitosan-grafted graphene oxide/magnetic nanoparticle system for theranostic applications

Abstract

There is currently a great demand especially in cancer treatment for transformative theranostic technologies combining imaging with drug delivery. This study reports the design and optimization of a hybrid theranostic nano-system combining the imaging capabilities of magnetic nanoparticles (MNPs) with the great potential of chitosan-grafted graphene oxide (GO) as a pH-sensitive smart nano-carrier, using different molecular weights and concentrations of chitosan. The loading and release behavior, biocompatibility, and magnetic properties of the MNP/GO/chitosan nano-system were experimentaly evaluated with a chemottherapy drug, Doxorubicin through a range of analytical methods. Increased pH resulted in a reduction in the rate of doxorubicin release, suggesting the formation of hydrogen bonds and the physical prevention of collapsed chitosan chains. In addition, a decrease in chitosan molecular weight, and an increase in concentration reduced the doxorubicin loading in around 24% yet a decrease in molecular weight increased the released amount in more than 200%. This has been related to fewer hydrogen binding and more contribution of π-π stacking in doxorubicin-chitosan interactions. The T2 contrast efficacy increased by grafting MNP/GO with high molecular weight chitosan due to the better surface coverage. Cytotoxicity assays with healthy L929 cell lines revealed high biocompatibility of MNP/GO/chitosan nano-system, suggesting chitosan prevents GO contact with the cell membrane. Further assays carried out with cancer cells MCF7 with MNP/GO/chitosan loaded with doxorubicin showed improved performance for MNP/GO grafted with low molecular weight chitosan. On the overall, the hybrid MNP/GO grafted with high molecular weight chitosan at 6.0 g/dl showed optimal properties for theranostic applications.