title: Fluorescent CSC models evidence that targeted nanomedicines improve treatment sensitivity of breast and colon cancer stem cells.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Drug Delivery and Targeting Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
authors.forename: Petra
authors.initials: P
authors.lastname: Gener
authors.affiliation: iMed.ULisboa, Research Institute for Medicines, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Luis Pleno
authors.initials: LP
authors.lastname: Gouveia
authors.affiliation: Drug Delivery and Targeting Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: Guillem Romero
authors.initials: GR
authors.lastname: Sabat
authors.affiliation: Drug Delivery and Targeting Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; iMed.ULisboa, Research Institute for Medicines, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Diana Fernandes
authors.initials: DF
authors.lastname: de Sousa Rafael
authors.affiliation: Drug Delivery and Targeting Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: Núria Bergadà
authors.initials: NB
authors.lastname: Fort
authors.affiliation: iMed.ULisboa, Research Institute for Medicines, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Arranja
authors.affiliation: Drug Delivery and Targeting Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain; Functional Validation and Preclinical Studies (FVPR), CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Fernández
authors.affiliation: Drug Delivery and Targeting Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: Rafael Miñana
authors.initials: RM
authors.lastname: Prieto
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain; Inmunobiology Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: Joan Sayos
authors.initials: JS
authors.lastname: Ortega
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain; Molecular Oncology Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Arango
authors.affiliation: Drug Delivery and Targeting Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain; Functional Validation and Preclinical Studies (FVPR), CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: Ibane
authors.initials: I
authors.lastname: Abasolo
authors.affiliation: iMed.ULisboa, Research Institute for Medicines, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Videira
authors.affiliation: Drug Delivery and Targeting Group, CIBBIM Nanomedicine, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. Electronic address: simo.schwartz@vhir.org.
authors.forename: Simo
authors.initials: S
authors.lastname: Schwartz
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D008823:Micelles; D008856:Microscopy, Fluorescence; D050997:Nanomedicine; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D050697:Retinal Dehydrogenase
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D005456:Fluorescent Dyes; D018960:Hyaluronan Receptors; D008823:Micelles; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel
keywords: Active targeting; Cancer stem cells; Nanomedicine