Biocompatible ELR-Based Polyplexes Coated with MUC1 Specific Aptamers and Targeted for Breast Cancer Gene Therapy

Producción Científica
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 character- ization 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.
Este trabajo forma parte de los Proyectos de Investigación financiados por la Comisión Europea a través del Fondo Social Europeo (FSE) y de la Consejería de Educación mediante el Fondo Europeo de Desarrollo Regional (ERDF), el MINECO (Proyectos MAT2013-41723-R, MAT2013-42473-R, PRI−PIBAR-2011-1403 y MAT2012-38043), la Junta de Castilla y León (Proyectos VA155A12, VA152A12, and VA244U13), el CIBER-BBN y el Instituto de Salud Carlos III mediante el Centro de Medicina Regenerativa y Terapia Celular de Castilla y León.