CuS@MOF-Based\nWell-Designed Quercetin Delivery System\nfor Chemo–Photothermal Therapy

Abstract

Quercetin\n(QT) is one promising candidate for the treatment of\nvarious cancers with virtually no toxic side effects. However, its\nanticancer effect is severely restricted by its poor bioavailability,\nlow water solubility, and chemical instability in the neutral and\nalkaline medium. Herein, zeolitic imidazolate framework-8 (ZIF-8)\nis first reported as the multifunctional nanoplatform to the codelivery\nof quercetin as an anticancer agent and CuS nanoparticles as a photothermal\ntherapy (PTT) agent for synergistic combination of chemotherapy and\nPTT as well as overcoming the drawbacks of quercetin. Moreover, folic\nacid–bovine serum albumin (FA–BSA) conjugates are applied\nto stabilize the CuS@ZIF-8-QT to promote the bioavailability of quercetin\nand realize active-targeting drug delivery. Near-infrared (NIR) fluorescent\nimaging demonstrated the highly increased drug accumulations of FA–BSA/CuS@ZIF-8-QT\nin tumors, resulting from efficient internalization via FA-receptors-mediated\nendocytosis. The results of in vivo and in vitro anticancer experiments\ndemonstrate that quercetin and PTT agent can work together efficiently\nunder NIR irradiation, thus remarkably improving the anticancer effect.\nTherefore, our newly designed FA–BSA/CuS@ZIF-8-QT multifunctional\ndrug delivery system might be a promising nanoplatform for cancer\ntreatment.