Effectiveness of 5-Fluorouracil and gemcitabine hydrochloride loaded iron‑based chitosan-coated MIL-100 composite as an advanced, biocompatible, pH-sensitive and smart drug delivery system on breast cancer therapy.

Abstract

This study was planned to evolve the bioavailability and therapeutic efficiency of Gemcitabine (GEM) and 5-Fluorouracil with decreased side effects using MIL-100 nano-composite as carrier. Impregnation approach was used for encapsulation of 5-Fluorouracil alone and with GEM inside the MIL-100. The formed 5-Fluorouracil@MIL-100 and 5-Fluorouracil-GEM@MIL-100 were then coated with chitosan, sequentially chelated with iron(III) and conjugated with quercetin, eventually obtaining a multifunctional MIL-100 nanocarrier. The hybrid nanocarrier nascency was verified by different characterization results. pH-sensitive releases of 5-Fluorouracil and GEM were observed because of the inherent pH-dependent stability of MIL-100. Additionally, we evaluated the anti-cancer activity of these nanocarriers through WST-1 analysis and acridine orange staining in MCF-7 human breast cancer and HUVEC control cell lines. Our findings showed that all nanocarriers exhibited anti-cancer activity and induced apoptosis in MCF-7 cells. However, 5-Fluorouracil@MIL-100 and chitosan-coated 5-Fluorouracil@MIL-100 with quercetin were more effective than other nanocarriers in MCF-7 cells (p<0.05). Moreover, we observed cytotoxicity in HUVEC cells due to the adverse side effects of chemotherapy drugs. However, chitosan coated nanocarriers with quercetin were less toxic on HUVEC cells at particularly 1µg/mL. Therefore, MIL-100 could be used for a promising chemotherapeutic drugs delivery and chitosan coated drugs with quercetin could be useful for reducing toxicity on normal cells.