Neutrophil Elastase Promotes Linker Cleavage and Paclitaxel Release from an Integrin-Targeted Conjugate.

Neutrophil Elastase Promotes Linker Cleavage and Paclitaxel Release from an Integrin-Targeted Conjugate.
Chemistry. 2018 Nov 19;:
Authors: Raposo Moreira Dias A, Pina A, Dean A, Lerchen HG, Caruso M, Gasparri F, Fraietta I, Troiani S, Arosio D, Belvisi L, Pignataro L, Dal Corso A, Gennari C
Abstract
We took advantage of one of the hallmarks of cancers, i.e. 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 αvβ3 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. In vitro linker cleavage assays and cell antiproliferative experiments demonstrate the efficacy of this tumor-targeting conjugate, opening the way to potential therapeutic applications.
PMID: 30452790 [PubMed - as supplied by publisher]

Source: Chemistry - November 19, 2018 Category: Chemistry Authors: Raposo Moreira Dias A, Pina A, Dean A, Lerchen HG, Caruso M, Gasparri F, Fraietta I, Troiani S, Arosio D, Belvisi L, Pignataro L, Dal Corso A, Gennari C Tags: Chemistry Source Type: research