Home > Articles > Published articles > Nanostructured toxins for the selective destruction of drug-resistant human CXCR4+ colorectal cancer stem cells |
Date: | 2020 |
Abstract: | Current therapies fail to eradicate colorectal Cancer Stem Cells (CSCs). One of the proposed reasons for this failure is the selection, by chemotherapy exposure, of resistant cells responsible for tumor recurrence. In this regard, CXCR4 overexpression in tumor associates with resistance and poor prognosis in colorectal cancer (CRC) patients. In this study, the effectiveness of engineered CXCR4-targeted self-assembling toxin nanoparticles has been explored in the selective killing of CXCR4 human colon-CSCs compared to 5-Fluorouracil and Oxaliplatin, both classical CRC chemotherapeutic agents. To assess this, 3D spheroid colon-CSCs cultures directly derived from CRC patients and CRC-CSC spheroid-derived tumor mouse models were developed. In these animal models, nanostructured toxins show highly selective induction of pyroptosis in the absence of apoptosis, thus having a great potential to overcome tumor resistance, since the same tumor models show resistance to chemotherapeutics. Results set the basis for further development of more efficient therapies focused on selective CXCR4 CSCs elimination activating non-apoptotic mechanisms and represent a pre-clinical proof of concept for the use of CSCs-targeted nanostructured toxins as protein drugs for CRC therapy. |
Grants: | Ministerio de Ciencia e Innovación BIO2016-76063-R Instituto de Salud Carlos III PI15/00378 Instituto de Salud Carlos III PIE15/00028 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/FI_B100063 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-865 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-132 |
Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Language: | Anglès |
Document: | Article ; recerca ; Versió acceptada per publicar |
Subject: | Protein nanoparticles ; Genetic engineering ; Self-assembling ; Drug delivery ; Cancer stem cells ; Cell signaling |
Published in: | Journal of Controlled Release, Vol. 320 (April 2020) , p. 96-104, ISSN 1873-4995 |
Article. Postprint 26 p, 2.2 MB |
Figures 9 p, 2.2 MB |