PH-responsive and targeted delivery of rutin for breast cancer therapy via folic acid-functionalized carbon dots

Abstract

Here, first we have synthesized carbon dots (CDs) from red Korean ginseng, and modified further with folic acid (FA) for the targeted and controlled delivery of a natual flavonoid, rutin (RUT). FA conjugated and morin loaded CDs (FA-CDs-RUT) displayed size ~70 nm, drug loading content of 14.5 % and a pH-dependent drug release behaviour. Human breast cancer MCF-7 cells were taken for checking the anticancer activities of FA-CDs-RUT. The nanohybrids (FA-CDs-RUT) showed a dose-dependent (10–50 μg/mL) cytotoxicity in MCF-7 cells and caused apoptotic cell death by inducing oxidative stress and mitochondrial damage. Besides, anti-migratory role of FA-CDs-RUT was also observed. The in vivo intravenous (i.v.) administration of FA-CDs-RUT nanohybrid was found to effectively decrease the tumor growth in tumor-bearing mice as compared with bare rutin and CDs. Interestingly, none of the nanoformulations and bare rutin caused any significant alterations in blood biochemical parameters. The enhanced anticancer activity of FA-CDs-RUT is thought to be due to combinatorial anticancer effects of CDs and rutin. We also performed docking study of rutin with Bcl-2 to gain insights into possible pathways of cell growth regulation. Molecular docking study shown that rutin binds with Bcl-2 with binding affinity of −7.6 k Cal/mol. Together, this study provides insight into the usability of FA-CDs-RUT to treat breast cancer with their mechanisms of action.