Home > Articles > Published articles > Biparatopic protein nanoparticles for the precision therapy of cxcr4+ cancers |
Date: | 2021 |
Abstract: | The accumulated molecular knowledge about human cancer enables the identification of multiple cell surface markers as highly specific therapeutic targets. A proper tumor targeting could significantly avoid drug exposure of healthy cells, minimizing side effects, but it is also expected to increase the therapeutic index. Specifically, colorectal cancer has a particularly poor prognosis in late stages, being drug targeting an appropriate strategy to substantially improve the therapeutic efficacy. In this study, we have explored the potential of the human albumin-derived peptide, EPI-X4, as a suitable ligand to target colorectal cancer via the cell surface protein CXCR4, a chemokine receptor overexpressed in cancer stem cells. To explore the potential use of this ligand, self-assem-bling protein nanoparticles have been generated displaying an engineered EPI-X4 version, which conferred a modest CXCR4 targeting and fast and high level of cell apoptosis in tumor CXCR4 cells, in vitro and in vivo. In addition, when EPI-X4-based building blocks are combined with biologically inert polypeptides containing the CXCR4 ligand T22, the resulting biparatopic nanoparticles show a dramatically improved biodistribution in mouse models of CXCR4 human cancer, faster cell internalization and enhanced target cell death when compared to the version based on a single ligand. The generation of biparatopic materials opens exciting possibilities in oncotherapies based on high precision drug delivery based on the receptor CXCR4. |
Grants: | Agencia Estatal de Investigación PID2019-105416RB-I00 Ministerio de Ciencia e Innovación FPU18/04615 Ministerio de Economía y Competitividad BIO2016-76063-R Instituto de Salud Carlos III PIE15/00028 Instituto de Salud Carlos III PI18/00650 Instituto de Salud Carlos III CP19/00028 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018/FI_B2_00051 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-865 |
Note: | Altres ajuts: CIBER-BBN (project NANOPROTHER), CIBER-BBN project 4NanoMets i CIBER-BBN project NANOREMOTE. EU COST Action CA 17140 |
Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Subject: | Tumor homing ; EPI-X4; CXCR4 ; Biparatopic nanoparticles ; Tumor targeting ; Drug delivery |
Published in: | Cancers, Vol. 13, issue 12 (June 2021) , art. 2929, ISSN 2072-6694 |
17 p, 7.9 MB |