Polydepsipeptide Block-Stabilized Polyplexes for Efficient Transfection of Primary Human Cells.

Abstract:

:The rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an Mn ∼ 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60-150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer to primary human cells.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Wang W,Naolou T,Ma N,Deng Z,Xu X,Mansfeld U,Wischke C,Gossen M,Neffe AT,Lendlein A

doi

10.1021/acs.biomac.7b01034

subject

Has Abstract

pub_date

2017-11-13 00:00:00

pages

3819-3833

issue

11

eissn

1525-7797

issn

1526-4602

journal_volume

18

pub_type

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