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Abstract Title:

Development of quercetin-loaded PVCL-PVA-PEG micelles and application in inhibiting tumor angiogenesis through the PI3K/Akt/VEGF pathway.

Abstract Source:

Toxicol Appl Pharmacol. 2022 Jan 21 ;437:115889. Epub 2022 Jan 21. PMID: 35065992

Abstract Author(s):

Xueju Qi, Cong Gao, Chuanjin Yin, Junting Fan, Xiaochen Wu, Guohu Di, Jing Wang, Chuanlong Guo

Article Affiliation:

Xueju Qi

Abstract:

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 demonstratepotential for the delivery of poorly soluble drugs for tumor treatment.

Study Type : In Vitro Study

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