Different types of degradable vectors from low-molecular-weight polycation-functionalized poly(aspartic acid) for efficient gene delivery

X B Dou; Y Hu; N N Zhao; F J Xu

doi:10.1016/j.biomaterials.2013.12.017

Different types of degradable vectors from low-molecular-weight polycation-functionalized poly(aspartic acid) for efficient gene delivery

Biomaterials. 2014 Mar;35(9):3015-26. doi: 10.1016/j.biomaterials.2013.12.017. Epub 2014 Jan 2.

Authors

X B Dou¹, Y Hu¹, N N Zhao¹, F J Xu²

Affiliations

¹ State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Carbon Fiber and Functional Polymers, Ministry of Education, Beijing Laboratory of Biomedical Materials, College of Materials Science & Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
² State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Carbon Fiber and Functional Polymers, Ministry of Education, Beijing Laboratory of Biomedical Materials, College of Materials Science & Engineering, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: xufj@mail.buct.edu.cn.

PMID: 24388816
DOI: 10.1016/j.biomaterials.2013.12.017

Abstract

Poly(aspartic acid) (PAsp) has been employed as the potential backbone for the preparation of efficient gene carriers, due to its low cytotoxicity, good biodegradability and excellent biocompatibility. In this work, the degradable linear or star-shaped PBLA was first prepared via ring-opining polymerization of β-benzyl-L-aspartate N-carboxy anhydride (BLA-NCA) initiated by ethylenediamine (ED) or ED-functionalized cyclodextrin cores. Then, PBLA was functionalized via aminolysis reaction with low-molecular-weight poly(2-(dimethylamino)ethyl methacrylate) with one terminal primary amine group (PDMAEMA-NH2), followed by addition of excess ED or ethanolamine (EA) to complete the aminolysis process. The obtained different types of cationic PAsp-based vectors including linear or star PAsp-PDM-NH2 and PAsp-PDM-OH exhibited good condensation capability and degradability, benefiting gene delivery process. In comparison with gold standard polyethylenimine (PEI, ∼ 25 kDa), the cationic PAsp-based vectors, particularly star-shaped ones, exhibited much better transfection performances.

Keywords: Degradable; Gene delivery; PAsp; PDMAEMA; Ring-opening polymerization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biophysical Phenomena
COS Cells
Chlorocebus aethiops
DNA / metabolism
Electrophoresis
Gene Transfer Techniques*
Hep G2 Cells
Humans
Magnetic Resonance Spectroscopy
Methacrylates / chemistry
Molecular Weight
Nylons / chemistry
Particle Size
Peptides / chemistry*
Plasmids / metabolism
Polyamines / chemistry*
Polyelectrolytes
Static Electricity

Substances

Methacrylates
Nylons
Peptides
Polyamines
Polyelectrolytes
poly(2-(dimethylamino)ethyl methacrylate)
polycations
polyaspartate
DNA