Magnetic UiO-66-NH(2) Core–Shell Nanohybrid as a Promising Carrier for Quercetin Targeted Delivery toward Human Breast Cancer Cells

[Image: see text] In this study, a magnetic core–shell metal–organic framework (MOF) nanocomposite, Fe(3)O(4)-COOH@UiO-66-NH(2), 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-NH(2) 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@Fe(3)O(4)-COOH@UiO-66-NH(2) 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-NH(2), Fe(3)O(4)-COOH, Fe(3)O(4)-COOH@UiO-66-NH(2), and QU@Fe(3)O(4)-COOH@UiO-66-NH(2). Treatment with QU@Fe(3)O(4)-COOH@UiO-66-NH(2) 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@Fe(3)O(4)-COOH@UiO-66-NH(2) by cancer cells and the induction of cancer cell death through the apoptosis pathway. These findings highlight the considerable potential of Fe(3)O(4)-COOH@UiO-66-NH(2) as a targeted nanocarrier for the delivery of anticancer drugs.