The Methylurolithin A-loaded PLGA-Folate-Chitosan Nanoparticles (Mu-PFCNPs), as the novel safe selective anti-colon cancer drug delivery system

Abstract

The synthesis of a targeted natural anticancer substitution has opened up a promising horizon by increasing the effectiveness of the treatment and reducing its undesirable side effects. However, the weak bio-accessibility and chemical instability of the medicinal plant phytochemicals are their main limitations. The nanospheres of poly lactic-co-glycolic acid (PLGA) is known to be safe due to its bioavailability and biodegradable profile. In the current study, Methylurolitin-A (MUA) was loaded into PLGA nanoparticles with folic acid-linked chitosan to investigate its antioxidant, anti-angiogenic, and anticancer activities. The MUA-loaded PLGA-folate-chitosan nanoparticles (Mu-PFCNPs) were synthesized and characterized by DLS, Zeta potential, FTIR, and FESEM. The Mu-PFCNPs’ antioxidant activity was analyzed by ABTS, DPPH, and FRAP assays followed by measuring the antioxidant gene expression. Moreover, the anti-angiogenic potential of the nanoparticles was evaluated on HT-29 cells by CAM assay, conducting the VEGF/VEGFR gene expression measurement. Finally, the Mu-PFCNP selective toxicity was studied on the HT-29, A2780, PANC, and HepG2 cancer cell lines utilizing MTT assay. The nanoparticles (+30.14mV, 134nm) exhibited potent antioxidant activity and overexpressed SOD and Catalase genes in treated HT-29 cells. Mu-PFCNPs down regulated VEGF and VEGFR gene expression on HT-29 cells. Additionally, the CAM results verified the activity by indicating the reduction in the number of blood vessels. Finally, Mu-PFCNPs induced a significant selective cytotoxic impact on HT-29 cancer cells compared to other cancer cell lines. The antioxidant, anti-angiogenic and therefore anti-colon cancer activities of Mu-PFCNPs make them a suitable targeted anti-cancer compound, particularly for the treatment of human colon cancer.