School of Pharmaceutical Science, Key Laboratory of Chemical Biology, Ministry of Education , Shandong University , Jinan 250012 , China.
Key Lab of Colloid & Interface Chemistry, Ministry of Education , Shandong University , Jinan 250100 , China.
ACS Appl Mater Interfaces. 2018 Oct 10;10(40):34513-34523. doi: 10.1021/acsami.8b13487. Epub 2018 Sep 26.
Quercetin (QT) is one promising candidate for the treatment of various cancers with virtually no toxic side effects. However, its anticancer effect is severely restricted by its poor bioavailability, low water solubility, and chemical instability in the neutral and alkaline medium. Herein, zeolitic imidazolate framework-8 (ZIF-8) is first reported as the multifunctional nanoplatform to the codelivery of quercetin as an anticancer agent and CuS nanoparticles as a photothermal therapy (PTT) agent for synergistic combination of chemotherapy and PTT as well as overcoming the drawbacks of quercetin. Moreover, folic acid-bovine serum albumin (FA-BSA) conjugates are applied to stabilize the CuS@ZIF-8-QT to promote the bioavailability of quercetin and realize active-targeting drug delivery. Near-infrared (NIR) fluorescent imaging demonstrated the highly increased drug accumulations of FA-BSA/CuS@ZIF-8-QT in tumors, resulting from efficient internalization via FA-receptors-mediated endocytosis. The results of in vivo and in vitro anticancer experiments demonstrate that quercetin and PTT agent can work together efficiently under NIR irradiation, thus remarkably improving the anticancer effect. Therefore, our newly designed FA-BSA/CuS@ZIF-8-QT multifunctional drug delivery system might be a promising nanoplatform for cancer treatment.
槲皮素(QT)是一种很有前途的治疗各种癌症的候选药物,几乎没有毒副作用。然而,由于其生物利用度差、水溶性低以及在中性和碱性介质中的化学不稳定性,其抗癌效果受到严重限制。在此,沸石咪唑酯骨架-8(ZIF-8)首次被报道为多功能纳米平台,用于共同递送槲皮素作为抗癌剂和 CuS 纳米粒子作为光热治疗(PTT)剂,以协同化疗和 PTT 以及克服槲皮素的缺点。此外,应用叶酸-牛血清白蛋白(FA-BSA)缀合物来稳定 CuS@ZIF-8-QT,以提高槲皮素的生物利用度并实现主动靶向药物递送。近红外(NIR)荧光成像显示,FA-BSA/CuS@ZIF-8-QT 在肿瘤中的药物积累显著增加,这是由于通过 FA 受体介导的内吞作用实现了高效内化。体内和体外抗癌实验的结果表明,在近红外照射下,槲皮素和 PTT 剂可以有效地协同作用,从而显著提高抗癌效果。因此,我们新设计的 FA-BSA/CuS@ZIF-8-QT 多功能药物递送系统可能是癌症治疗的一种有前途的纳米平台。