Neutrophil Elastase Promotes Linker Cleavage and Paclitaxel Release from an Integrin-Targeted Conjugate.
Chemistry
; 25(7): 1696-1700, 2019 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-30452790
ABSTRACT
This work takes advantage of one of the hallmarks of cancer, that is, the presence of tumor infiltrating cells of the immune system and leukocyte-secreted enzymes, to promote the activation of an anticancer drug at the tumor site. The peptidomimetic integrin ligand cyclo(DKP-RGD) was found to accumulate on the surface of αv ß3 integrin-expressing human renal cell carcinoma 786-O cells. The ligand was conjugated to the anticancer drug paclitaxel through a Asn-Pro-Val (NPV) tripeptide linker, which is a substrate of neutrophil-secreted elastase. Inâ
vitro linker cleavage assays and cell antiproliferative experiments demonstrate the efficacy of this tumor-targeting conjugate, opening the way to potential therapeutic applications.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paclitaxel
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Elastase de Leucócito
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Integrina alfaVbeta3
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article