ATP-Responsive Low-Molecular-Weight Polyethylenimine-Based Supramolecular Assembly via Host-Guest Interaction for Gene Delivery.

Abstract:

:In this work, we report on an ATP-responsive low-molecular-weight polyethylenimine (LMW-PEI)-based supramolecular assembly. It formed via host-guest interaction between PEI (MW = 1.8 kDa)-α-cyclodextrin (α-CD) conjugates and PEI1.8k-phenylboronic acid (PBA) conjugates. The host-guest interaction between PEI1.8k-α-CD and PEI1.8k-PBA was confirmed by the 2D-NOESY chromatogram experiment and competition test. The ATP-responsive property of the supramolecular assembly was evaluated by a series of ATP-triggered degradation and siRNA release studies in terms of fluorescence resonance energy transfer, agarose gel electrophoresis assay, and the time course monitoring of the particle size and morphology. Confocal laser scanning microscopy confirmed the intracellular disassembly of the supramolecular polymer and the release of siRNA. The supramolecular assembly showed high buffering capability and was capable of protecting siRNA from RNase degradation. It had high cytocompatibility according to in vitro cytotoxicity and hemolysis assays. LMW-PEI-based supramolecular assembly facilitated cellular entry of siRNA via energy-dependent endocytosis. Moreover, the assembly/SR-A siRNA polyplexes at N/P ratio of 30 was most effective in knocking down SR-A mRNA and inhibiting uptake of modified LDL. Taken together, this work shows that ATP-responsive LMW-PEI-based supramolecular assembly is a promising gene vector and has potential application in treating atherosclerosis.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Jiang C,Qi Z,Jia H,Huang Y,Wang Y,Zhang W,Wu Z,Yang H,Liu J

doi

10.1021/acs.biomac.8b01395

subject

Has Abstract

pub_date

2019-01-14 00:00:00

pages

478-489

issue

1

eissn

1525-7797

issn

1526-4602

journal_volume

20

pub_type

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