Anisamide-functionalized pH-responsive amphiphilic chitosan-based paclitaxel micelles for sigma-1 receptor targeted prostate cancer treatment.
Carbohydr Polym
; 229: 115498, 2020 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-31826492
Controlled release and tumor-selective distribution are highly desirable for anticancer nanomedicines. Here, we design and synthesize an anisamide-conjugated N-octyl-N,O-maleoyl-O-phosphoryl chitosan (a-OMPC) which can form amphiphilic micelles featuring pH-responsive release and high affinity to sigma-1 receptor-overexpressed tumors for paclitaxel (PTX) delivery. Thereinto, maleoyl and phosphoryl groups cooperatively contribute to pH-responsive drug release due to a conversion from hydrophile to hydrophobe in the acidic microenvironment of endo/lysosomes. We demonstrated that PTX-loaded a-OMPC micelles (PTX-aM) enhanced the cellular internalization via the affinity between anisamide and sigma-1 receptor, rapidly released drug in endo/lysosomes and elevated the cytotoxicity against PC-3 cells. The in vivo studies further verified that PTX-aM could largely accumulate at the tumor site even after 24 h of administration, resulting in obvious inhibition effect and prolonged survival period in PC-3 tumor xenograft-bearing mice. Moreover, OMPC showed no obvious hemolytic and acute toxicity. Collectively, this chitosan derivate holds a promising potential in application of prostate cancer-targeted drug delivery system.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Paclitaxel
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Receptores sigma
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Quitosana
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Terapia de Alvo Molecular
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Interações Hidrofóbicas e Hidrofílicas
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Carbohydr Polym
Ano de publicação:
2020
Tipo de documento:
Article