Endoplasmic reticulum-targeted glutathione and pH dual responsive vitamin lipid nanovesicles for tocopheryl DM1 delivery and cancer therapy.
Int J Pharm
; 582: 119331, 2020 May 30.
Article
em En
| MEDLINE
| ID: mdl-32289484
ABSTRACT
The major drawbacks of the cytotoxin like DM1 are the off-target effects. Here, the targeting nanovesicles were developed by synthesizing tocopherol-SS-DM1 and conjugating a pH low insertion peptide (pHLIP) to PEGylated phospholipids, in which tocopherol-SS-DM1 improves the drug loading and is glutathione responsive in the cytoplasm, meanwhile, the pH insertion peptide targets the acidic microenvironment of cancer cells. Besides, these nanovesicles can accumulate at the endoplasmic reticulum and show increased cancer therapeutic effects both in vitro and in vivo. These targeting nanovesicles provide a novel formulation for subcellular organelle targeting, a platform for precisely delivery of cytotoxic DM1 to cancer cells, and an alternative strategy for antibody-drug conjugates (ADCs).
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
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Pró-Fármacos
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Tocoferóis
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Retículo Endoplasmático
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Nanopartículas
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Glutationa
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Lipídeos
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Maitansina
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Proteínas de Membrana
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Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China