title: Biocompatible ELR-Based Polyplexes Coated with MUC1 Specific Aptamers and Targeted for Breast Cancer Gene Therapy.
abstract: The search for new and biocompatible materials with high potential for improvement is a challenge in gene delivery applications. A cell type specific vector made of elastin-like recombinamer (ELR) and aptamers has been specifically designed for the intracellular delivery of therapeutic material for breast cancer therapy. A lysine-enriched ELR was constructed and complexed with plasmid DNA to give positively charged and stable polyplexes. Physical characterization of these polyplexes showed a particle size of around 140 nm and a zeta potential of approximately +40 mV. The incorporation of MUC1-specific aptamers into the polyplexes resulted in a slight decrease in zeta potential but increased cell transfection specificity for MCF-7 breast cancer cells with respect to a MUC1-negative tumor line. After showing the transfection ability of this aptamer-ELR vector which is facilitated mainly by macropinocytosis uptake, we demonstrated its application for suicide gene therapy using a plasmid containing the gene of the toxin PAP-S. The strategy developed in this work about using ELR as polymeric vector and aptamers as supplier of specificity to deliver therapeutic material into MUC1-positive breast cancer cells shows promising potential and continues paving the way for ELRs in the biomedical field.
authors.affiliation: Bioforge Research Group, CIBER-BBN, University of Valladolid , LUCIA, Paseo de Belén 19, 47011 Valladolid, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Piña
authors.affiliation: Bioforge Research Group, CIBER-BBN, University of Valladolid , LUCIA, Paseo de Belén 19, 47011 Valladolid, Spain.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Girotti
authors.affiliation: Bioforge Research Group, CIBER-BBN, University of Valladolid , LUCIA, Paseo de Belén 19, 47011 Valladolid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Santos
authors.affiliation: Bioforge Research Group, CIBER-BBN, University of Valladolid , LUCIA, Paseo de Belén 19, 47011 Valladolid, Spain.
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Rodríguez-Cabello
authors.affiliation: Bioforge Research Group, CIBER-BBN, University of Valladolid , LUCIA, Paseo de Belén 19, 47011 Valladolid, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Arias
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002470:Cell Survival; D002478:Cells, Cultured; D004549:Elastin / Q000737:chemistry*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D058990:Molecular Targeted Therapy; D018396:Mucin-1 / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011108:Polymers / Q000737:chemistry*
chemical_list: D052157:Aptamers, Nucleotide; D001672:Biocompatible Materials; C060192:MUC1 protein, human; D018396:Mucin-1; D011108:Polymers; D004549:Elastin
keywords: ELR; aptamer; breast cancer; polyplex; transfection