title: Multifunctionalized iron oxide nanoparticles for selective drug delivery to CD44-positive cancer cells.
abstract: Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully  apply these novel therapeutic approaches, efforts are focused on the biological functionalization of the nanoparticles to improve the selectivity towards cancer cells. In this work, we present the synthesis and characterization of novel multifunctionalized iron oxide magnetic nanoparticles (MNPs) with antiCD44 antibody and gemcitabine derivatives, and their application for the selective treatment of CD44-positive cancer cells. The lymphocyte homing receptor CD44 is overexpressed in a large variety of cancer cells, but also in cancer stem cells (CSCs) and circulating tumor cells (CTCs). Therefore, targeting CD44-overexpressing cells is a challenging and promising anticancer strategy. Firstly, we demonstrate the targeting of antiCD44 functionalized MNPs to different CD44-positive cancer cell lines using a CD44-negative non-tumorigenic cell line as a control, and verify the specificity by ultrastructural characterization and downregulation of CD44 expression. Finally, we show the selective drug delivery potential of the MNPs by the killing of CD44-positive cancer cells using a CD44-negative non-tumorigenic cell line as a control. In conclusion, the proposed multifunctionalized MNPs represent an excellent biocompatible nanoplatform for selective CD44-positive cancer therapy in vitro.
authors.affiliation: Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Campus de Cantoblanco, 28049 Madrid, Spain. CNB-CSIC-IMDEA Nanociencia Associated Unit, Cantoblanco, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Aires
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Ocampo
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Simões
authors.forename: María
authors.initials: M
authors.lastname: Josefa Rodríguez
authors.forename: Jael F
authors.initials: JF
authors.lastname: Cadenas
authors.forename: Pierre
authors.initials: P
authors.lastname: Couleaud
authors.forename: Katherine
authors.initials: K
authors.lastname: Spence
authors.forename: Alfonso
authors.initials: A
authors.lastname: Latorre
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Miranda
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Somoza
authors.forename: Robert B
authors.initials: RB
authors.lastname: Clarke
authors.forename: José L
authors.initials: JL
authors.lastname: Carrascosa
authors.forename: Aitziber L
authors.initials: AL
authors.lastname: Cortajarena
mesh_terms: D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005290:Ferric Compounds / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008280:Magnetics / Q000379:methods; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D014018:Tissue Distribution / Q000502:physiology; D000093542:Gemcitabine
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; D018960:Hyaluronan Receptors; D003841:Deoxycytidine; C000499:ferric oxide; D000093542:Gemcitabine