Fluorescent CSC models evidence that targeted nanomedicines improve treatment sensitivity of breast and colon cancer stem cells

• Published in: Nanomedicine 2015-11, Vol.11 (8), p.1883-1892
• Main Authors: Gener, Petra, PhD, Gouveia, Luis Pleno, MSc, Sabat, Guillem Romero, MSc, de Sousa Rafael, Diana Fernandes, MSc, Fort, Núria Bergadà, MSc, Arranja, Alexandra, MSc, Fernández, Yolanda, PhD, Prieto, Rafael Miñana, MSc, Ortega, Joan Sayos, PhD, Arango, Diego, PhD, Abasolo, Ibane, PhD, Videira, Mafalda, PhD, Schwartz, Simo, MD, PhD
• Format: Article
• Language: English
• Subjects: Active targeting; Aldehyde Dehydrogenase - genetics; Aldehyde Dehydrogenase 1 Family; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer stem cells; Cell Line, Tumor; Colonic Neoplasms - drug therapy; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Drug Carriers - chemistry; Drug Delivery Systems - methods; ErbB Receptors - analysis; Female; Fluorescent Dyes - analysis; Fluorescent Dyes - metabolism; Genes, Reporter; Humans; Hyaluronan Receptors - analysis; Internal Medicine; Micelles; Microscopy, Fluorescence; Nanomedicine; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; Paclitaxel - administration & dosage; Paclitaxel - pharmacology; Polyethylene Glycols - chemistry; Polyglactin 910 - chemistry; Retinal Dehydrogenase
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2015.07.009

Abstract To be able to study the efficacy of targeted nanomedicines in marginal population of highly aggressive cancer stem cells (CSC), we have developed a novel in vitro fluorescent CSC model that allows us to visualize these cells in heterogeneous population and to monitor CSC biological performance after therapy. In this model tdTomato reporter gene is driven by CSC specific (ALDH1A1) promoter and contrary to other similar models, CSC differentiation and un-differentiation processes are not restrained and longitudinal studies are feasible. We used this model for preclinical validation of poly[( d , l -lactide-co-glycolide)-co-PEG] (PLGA- co -PEG) micelles loaded with paclitaxel. Further, active targeting against CD44 and EGFR receptors was validated in breast and colon cancer cell lines. Accordingly, specific active targeting toward surface receptors enhances the performance of nanomedicines and sensitizes CSC to paclitaxel based chemotherapy. From the Clinical Editor Many current cancer therapies fail because of the failure to target cancer stem cells. This surviving population soon proliferates and differentiates into more cancer cells. In this interesting article, the authors designed an in vitro cancer stem cell model to study the effects of active targeting using antibody-labeled micelles containing chemotherapeutic agent. This new model should allow future testing of various drug/carrier platforms before the clinical phase.