Oligopeptide-terminated poly(β-amino ester)s for highly efficient gene delivery and intracellular localization

被引：76

作者：

Segovia, Nathaly ^{[1
]}

Dosta, Pere ^{[1
]}

Cascante, Anna ^{[1
]}

Ramos, Victor ^{[1
]}

Borros, Salvador ^{[1
]}

机构：

[1] Univ Ramon Llull, Inst Quim Sarria, Grp Engn Mat GEMAT, Barcelona 08017, Spain

来源：

ACTA BIOMATERIALIA | 2014年 / 10卷 / 05期

关键词：

Polyplexes Gene delivery; Non-viral systems; Poly(beta-amino ester)s; Nanoparticle; MICHAEL ADDITION-REACTIONS; ARGININE-RICH PEPTIDES; IN-VITRO; TRANSFECTION EFFICIENCY; PARALLEL SYNTHESIS; POLYMER LIBRARY; NONVIRAL VECTOR; STEM-CELLS; NANOPARTICLES; THERAPY;

D O I：

10.1016/j.actbio.2013.12.054

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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(beta-amino ester)s (pBAE) containing terminal oligopeptides. The authors developed oligopeptide-modified pBAE-pDNA nanopartides 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. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

引用

页码：2147 / 2158

页数：12

共 74 条

[11] The characteristics and transfection efficiency of PEI modified by biodegradable poly(β-amino ester) [J].

Cherng, Jong-Yuh ;

Lee, Yuan-Po ;

Lin, Chao-Hsien ;

Chang, Kui-Hsiang ;

Chang, Wei-Yang ;

Shau, Min-Da .

JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 2010, 21 (05) :1543-1551

[12]

Cho EC, 2011, NAT NANOTECHNOL, V6, P385, DOI [10.1038/NNANO.2011.58, 10.1038/nnano.2011.58]

[13] Enhanced transfection efficiency of PAMAM dendrimer by surface modification with L-arginine [J].

Choi, JS ;

Nam, K ;

Park, J ;

Kim, JB ;

Lee, JK ;

Park, J .

JOURNAL OF CONTROLLED RELEASE, 2004, 99 (03) :445-456

[14] Design of modular non-viral gene therapy vectors [J].

De Laporte, L ;

Rea, JC ;

Shea, LD .

BIOMATERIALS, 2006, 27 (07) :947-954

[15] Polymers for DNA delivery [J].

Eliyahu, H ;

Barenholz, Y ;

Domb, AJ .

MOLECULES, 2005, 10 (01) :34-64

[16]

FELGNER JH, 1994, J BIOL CHEM, V269, P2550

[17] Improved cationic lipid formulations for in vivo gene therapy [J].

Felgner, PL ;

Tsai, YJ ;

Sukhu, L ;

Wheeler, CJ ;

Manthorpe, M ;

Marshall, J ;

Cheng, SH .

DNA VACCINES: A NEW ERA IN VACCINOLOGY, 1995, 772 :126-139

[18] In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. [J].

Fischer, D ;

Li, YX ;

Ahlemeyer, B ;

Krieglstein, J ;

Kissel, T .

BIOMATERIALS, 2003, 24 (07) :1121-1131

[19] Stearylated arginine-rich peptides: A new class of transfection systems [J].

Futaki, S ;

Ohashi, W ;

Suzuki, T ;

Niwa, M ;

Tanaka, S ;

Ueda, K ;

Harashima, H ;

Sugiura, Y .

BIOCONJUGATE CHEMISTRY, 2001, 12 (06) :1005-1011

[20] Nanoparticles for Gene Transfer to Human Embryonic Stem Cell Colonies [J].

Green, Jordan J. ;

Zhou, Betty Y. ;

Mitalipova, Maisam M. ;

Beard, Caroline ;

Langer, Robert ;

Jaenisch, Rudolf ;

Anderson, Daniel G. .

NANO LETTERS, 2008, 8 (10) :3126-3130

← 1 2 3 4 5 6 7 8 →