Novel cationic cellulose-based nanocomposites for targeted delivery of methotrexate to breast cancer cells

Abstract

In this study, new smart zinc oxide (ZnO) and magnetic (Fe₃O₄) nanocarrier based on microcrystalline cellulose with functional cationic groups were developed by the combination of the grafting-onto method and reversible addition fragmentation chain transfer polymerization method. The synthesized nanocarriers were step by step validated and characterized using ¹H NMR, FTIR, VSM, TGA, DLS, and SEM-EDX analysis. The resulting NCs were uniform spherical NCs with a mean diameter of less than 70 nm. Methotrexate (MTX) was selectively attached to nanocarrier by ionic interaction with cationic part of nanoparticles and complexing with inorganic metal oxide part of NCs (high encapsulation efficiency of >98%). This NC–MTX conjugated system was used for targeted therapy of breast cancer cell line (MCF7). The cytotoxicity studies revealed high antitumor efficacy of MTX-ZnO NCs compared to MTX-Fe₃O₄ NCs and free MTX in MCF7 breast cancer cell lines due to high interaction of ZnO with MTX proved by DAPI staining and MTT assay. The formation of the complexes between the MTX and ZnO nanoparticles, lead to more sustainer drug release and enhanced chemotherapy efficiency by increasing the intracellular concentration of MTX.

Keywords:

• Chemotherapy
• RAFT polymerization
• methotrexate
• zinc oxide and magnetic nanocarriers
• cellulose

Acknowledgments

The author expresses their gratitude to Drug Applied Research Center. Tabriz University of Medical Sciences, for financially supporting of this project.

Additional information

Funding

The authors thanked for the “Iran National Science Foundation” (INSF) (grant No. INSF 90007920) for financial support of this project.