title: Oligopeptide-terminated poly(β-amino ester)s for highly efficient gene delivery and intracellular localization.
abstract: The main limitation of gene therapy towards clinics is the lack of robust, safe and efficient gene delivery vectors. This paper describes new polycations for gene delivery based on poly(β-amino ester)s (pBAE) containing terminal oligopeptides. The authors developed oligopeptide-modified pBAE-pDNA nanoparticles that achieve better cellular viability and higher transfection efficacy than other end-modified pBAE and commercial transfection agents. Gene expression in highly permissive cell lines was remarkably high, but transfection efficiency in less-permissive cell lines was highly dependent on oligopeptide composition and nanoparticle formulation. Moreover, the use of selected oligopeptides in the pBAE formulation led to preferential intracellular localization of the particles. Particle analysis of highly efficient pBAE formulations revealed different particle sizes and charge features, which indicates chemical pseudotyping of the particle surface, related to the oligopeptide chemical nature. In conclusion, chemical modification at the termini of pBAE with amine-rich oligopeptides is a powerful strategy for developing delivery systems for future gene therapy applications.
authors.affiliation: Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain.
authors.forename: Nathaly
authors.initials: N
authors.lastname: Segovia
authors.affiliation: Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Dosta
authors.affiliation: Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Cascante
authors.affiliation: Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain. Electronic address: victor.ramos@iqs.url.edu.
authors.forename: Victor
authors.initials: V
authors.lastname: Ramos
authors.affiliation: Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain. Electronic address: salvador.borros@iqs.url.edu.
authors.forename: Salvador
authors.initials: S
authors.lastname: Borrós
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D024202:Electrophoretic Mobility Shift Assay; D004705:Endocytosis; D005456:Fluorescent Dyes / Q000378:metabolism; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D011522:Protons; D013057:Spectrum Analysis; D055672:Static Electricity; D014162:Transfection
chemical_list: D005456:Fluorescent Dyes; D009842:Oligopeptides; D011108:Polymers; D011522:Protons; C507253:poly(beta-amino ester); D049452:Green Fluorescent Proteins
keywords: Gene delivery; Nanoparticle; Non-viral systems; Poly(β-amino ester)s; Polyplexes