Faculty Collaboration Database

ATP-Responsive Low-Molecular-Weight Polyethylenimine-Based Supramolecular Assembly via Host-Guest Interaction for Gene Delivery. Biomacromolecules 2019 Jan 14;20(1):478-489

Date

12/06/2018

Pubmed ID

30516950

DOI

10.1021/acs.biomac.8b01395

Scopus ID

2-s2.0-85058880227 (requires institutional sign-in at Scopus site)   38 Citations

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 PEI_1.8k-phenylboronic acid (PBA) conjugates. The host-guest interaction between PEI_1.8k-α-CD and PEI_1.8k-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.

Author List

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

Author

Hu Yang PhD Chair, Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Boronic Acids
Cells, Cultured
Cyclodextrins
Endocytosis
Gene Transfer Techniques
Hemolysis
Mice
Nanoconjugates
Polyethyleneimine
RAW 264.7 Cells
RNA, Small Interfering
Rabbits