Development of quercetin-loaded PVCL-PVA-PEG micelles and application in inhibiting tumor angiogenesis through the PI3K/Akt/VEGF pathway.
Toxicol Appl Pharmacol
; 437: 115889, 2022 02 15.
Article
em En
| MEDLINE
| ID: mdl-35065992
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 demonstrate potential for the delivery of poorly soluble drugs for tumor treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
/
Polímeros
/
Polivinil
/
Quercetina
/
Fosfatidilinositol 3-Quinases
/
Micelas
/
Neovascularização Patológica
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China