Neutrophil Elastase Promotes Linker Cleavage and Paclitaxel Release from an Integrin-Targeted Conjugate.
André Raposo Moreira DiasArianna PinaAmelia DeanHans-Georg LerchenMichele CarusoFabio GasparriIvan FraiettaSonia TroianiDaniela ArosioLaura BelvisiLuca PignataroAlberto Dal CorsoCesare GennariPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2018)
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 β3 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.
Keyphrases
- induced apoptosis
- cancer therapy
- cell cycle arrest
- renal cell carcinoma
- endothelial cells
- endoplasmic reticulum stress
- papillary thyroid
- signaling pathway
- single cell
- photodynamic therapy
- dna binding
- high throughput
- cell therapy
- cell adhesion
- oxidative stress
- emergency department
- cell death
- stem cells
- cell proliferation
- drug delivery
- anti inflammatory