Magnetic UiO-66-NH2 Core-Shell Nanohybrid as a Promising Carrier for Quercetin Targeted Delivery toward Human Breast Cancer Cells

ACS Omega. 2023 Oct 24;8(44):41321-41338. doi: 10.1021/acsomega.3c04863. eCollection 2023 Nov 7.

Abstract

In this study, a magnetic core-shell metal-organic framework (MOF) nanocomposite, Fe3O4-COOH@UiO-66-NH2, was synthesized for tumor-targeting drug delivery by incorporating carboxylate groups as functional groups onto ferrite nanoparticle surfaces, followed by fabrication of the UiO-66-NH2 shell using a facile self-assembly approach. The anticancer drug quercetin (QU) was loaded into the magnetic core-shell nanoparticles. The synthesized magnetic nanoparticles were comprehensively evaluated through multiple techniques, including FT-IR, PXRD, FE-SEM, TEM, EDX, BET, UV-vis, ZP, and VSM. Drug release investigations were conducted to investigate the release behavior of QU from the nanocomposite at two different pH values (7.4 and 5.4). The results revealed that QU@Fe3O4-COOH@UiO-66-NH2 exhibited a high loading capacity of 43.1% and pH-dependent release behavior, maintaining sustained release characteristics over a prolonged duration of 11 days. Furthermore, cytotoxicity assays using the human breast cancer cell line MDA-MB-231 and the normal cell line HEK-293 were performed to evaluate the cytotoxic effects of QU, UiO-66-NH2, Fe3O4-COOH, Fe3O4-COOH@UiO-66-NH2, and QU@Fe3O4-COOH@UiO-66-NH2. Treatment with QU@Fe3O4-COOH@UiO-66-NH2 substantially reduced the cell viability in cancerous MDA-MB-231 cells. Cellular uptake and cell death mechanisms were further investigated, demonstrating the internalization of QU@Fe3O4-COOH@UiO-66-NH2 by cancer cells and the induction of cancer cell death through the apoptosis pathway. These findings highlight the considerable potential of Fe3O4-COOH@UiO-66-NH2 as a targeted nanocarrier for the delivery of anticancer drugs.