Title

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.

Department(s)

Chemical and Biochemical Engineering

Comments

This work was supported by National Science and Technology Major Project of China (grant no. 2017YFA0205400) and National Natural Science Foundation of China (grant no. 81773669). The research was supported by Graduate Cultivation Innovative Project of Jiangsu Province (grant no. KYCX17Ì…0677) and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

This article is corrected by Correction: ATP-Responsive Low-Molecular-Weight Polyethylenimine-Based Supramolecular Assembly via Host-Guest Interaction for Gene Delivery (Biomacromolecules (2019) 20:1 (478-489) doi: 10.1021/Acs.biomac.8b01395).

Keywords and Phrases

Chromatographic analysis; Electrophoresis; Energy transfer; Fluorescence; Gene transfer; Genes; Molecular biology; Molecular weight; Particle size, Agarose gel electrophoresis; Buffering capabilities; Confocal laser scanning microscopy; Fluorescence resonance energy transfer; Host guest interactions; Particle size and morphologies; Supramolecular assemblies; Supramolecular polymers, Supramolecular chemistry, adenosine triphosphate; polyethyleneimine; ribonuclease; small interfering RNA; adenosine triphosphate; benzeneboronic acid; boronic acid derivative; cyclodextrin; nanoconjugate; polyethyleneimine, agar gel electrophoresis; Article; cellular distribution; comparative study; confocal laser scanning microscopy; controlled study; cytotoxicity; energy transfer; enzymatic degradation; fluorescence resonance energy transfer; gene targeting; hemolysis assay; human; human cell; in vitro study; lysosome; macrophage; molecular weight; nuclear Overhauser effect; particle size; priority journal; proton nuclear magnetic resonance; RAW 264.7 cell line; RNA degradation; static electricity; supramolecular chemistry; animal; cell culture; chemistry; drug effect; endocytosis; gene transfer; hemolysis; Leporidae; mouse, Adenosine Triphosphate; Animals; Boronic Acids; Cells, Cultured; Cyclodextrins; Endocytosis; Gene Transfer Techniques; Hemolysis; Mice; Nanoconjugates; Polyethyleneimine; Rabbits; RAW 264.7 Cells; RNA, Small Interfering

International Standard Serial Number (ISSN)

1525-7797; 1526-4602

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2019 American Chemical Society (ACS), All rights reserved.

Publication Date

14 Jan 2019

PubMed ID

30516950

Share

 
COinS