Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
The Third Affiliated Hospital of Shandong First Medical University, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan 250031, China.
Toxicol Appl Pharmacol. 2022 Feb 15;437:115889. doi: 10.1016/j.taap.2022.115889. Epub 2022 Jan 21.
Quercetin (Que) exhibits excellent biological activity; however, its clinical development is hindered owing to the poor water solubility. In this study, Que. was loaded on polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG, Soluplus) micelles through a thin-film hydration process, and their tumor angiogenesis inhibition ability was investigated. The particle size of Soluplus-Que micelles was 55.3 ± 1.8 nm, and the micelles stayed stability within 9 months. Soluplus-Que micelles can enhance the cell uptake of Que. and transport the micelles to intracellular lysosomes and mitochondria. The MTT assay results revealed that Soluplus-Que micelles enhanced the cytotoxicity of Que. on HUVEC cells. Furthermore, Soluplus-Que micelles inhibited migration and invasion of HUVEC cells, as well as inhibited the neovascularization of chick embryo allantoic membrane (CAM). The in vivo study revealed that Soluplus-Que micelles significantly inhibit the growth of H22 solid tumors, with low toxic side effects. Soluplus-Que inhibited the expression of CD31 (a marker of angiogenesis) and the PI3K/Akt/VEGF pathway in tumor tissues, indicating its potential to hold back tumor growth via the inhibition of angiogenesis. Our findings indicated that as a delivery system, Soluplus micelles demonstrate potential for the delivery of poorly soluble drugs for tumor treatment.
槲皮素（Que）具有优异的生物活性；然而，由于其水溶性差，其临床开发受到阻碍。在这项研究中，Que 通过薄膜水化过程负载在聚乙烯吡咯烷酮-醋酸乙烯酯-聚乙二醇接枝共聚物（PVCL-PVA-PEG，Soluplus）胶束上，并研究了它们的肿瘤血管生成抑制能力。Soluplus-Que 胶束的粒径为 55.3±1.8nm，并且在 9 个月内保持稳定。Soluplus-Que 胶束可以增强 Que 的细胞摄取，并将胶束转运到细胞内溶酶体和线粒体。MTT 测定结果表明，Soluplus-Que 胶束增强了 Que 对 HUVEC 细胞的细胞毒性。此外，Soluplus-Que 胶束抑制 HUVEC 细胞的迁移和侵袭，并抑制鸡胚尿囊膜（CAM）的新生血管形成。体内研究表明，Soluplus-Que 胶束显著抑制 H22 固体肿瘤的生长，且毒副作用低。Soluplus-Que 抑制了肿瘤组织中 CD31（血管生成的标志物）和 PI3K/Akt/VEGF 通路的表达，表明其通过抑制血管生成来抑制肿瘤生长的潜力。我们的研究结果表明，作为一种给药系统，Soluplus 胶束具有递送难溶性药物用于肿瘤治疗的潜力。
