Hypoxia-responsive folic acid conjugated glycol chitosan nanoparticle for enhanced tumor targeting treatment.
Int J Pharm
; 580: 119237, 2020 Apr 30.
Article
em En
| MEDLINE
| ID: mdl-32201251
ABSTRACT
Hypoxia is a characteristic feature of various ischemic diseases, including cancer. This study describes the development of glycol chitosan nanoparticles, hydrophobically modified with 4-nitrobenzyl chloroformate and folic acid (FA), that can specifically release drugs under hypoxic conditions. This hypoxia-responsive glycol chitosan nanoparticle conjugated with FA (HRGF) possesses tumor-targeting properties by virtue of conjugated FA and is able to release drugs in a nitroreductase (NTR)-dependent manner because its structure is cleaved by NTR under hypoxic conditions. HRGF nanoparticles showed improved in vivo cancer-targeting ability compared with HRG nanoparticles without FA. In vitro drug release profiles revealed that doxorubicin (DOX)-loaded HRGF (D@HRGF) nanoparticles showed rapid release under hypoxia conditions than normoxic conditions. In vitro cytotoxicity tests and microscopic observations showed that D@HRGF nanoparticles were more toxic towards hypoxic cells than normoxic cells, and that the release of DOX was more effective in hypoxia than normoxia. In vivo, D@HRGF nanoparticles showed more effective antitumor activity in mice compared with D@HRG and free DOX. Collectively, these results show that HRGF nanoparticles function as an effective drug-delivery system in hypoxic conditions. Moreover, these hypoxia-responsive nanoparticles would be effective not only in cancer, but also in other ischemic diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quitosana
/
Nanopartículas
/
Ácido Fólico
/
Hipóxia
/
Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2020
Tipo de documento:
Article