Issue 11, 2023

A catch-and-release nano-based gene delivery system


The design of nanomaterial-based nucleic acid formulations is one of the biggest endeavours in the search for clinically applicable gene delivery systems. Biopolymers represent a promising subclass of gene carriers due to their physicochemical properties, biodegradability and biocompatibility. By modifying melanin-like polydopamine nanoparticles with poly-L-arginine and poly-L-histidine blends, we obtained a novel catch-and-release gene delivery system for efficient trafficking of pDNA to human cells. A synergistic interplay of nanoparticle-bound poly-L-arginine and poly-L-histidine was observed and evaluated for pDNA binding affinity, cell viability, gene release and transfection. Although the functionalisation with poly-L-arginine was crucial for pDNA binding, the resulting nanocarriers failed to release pDNA intracellularly, resulting in limited protein expression. However, optimal pDNA release was achieved through the co-formulation with poly-L-histidine, essential for pDNA release. This effect enabled the design of gene delivery systems, which were comparable to Lipofectamine in terms of transfection efficacy and the catch-and-release surface modification strategy can be translated to other nanocarriers and surfaces.

Graphical abstract: A catch-and-release nano-based gene delivery system

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Article information

Article type
02 Jul 2023
05 Sep 2023
First published
06 Sep 2023
This article is Open Access
Creative Commons BY license

Nanoscale Horiz., 2023,8, 1588-1594

A catch-and-release nano-based gene delivery system

C. O. Franck, A. Bistrovic Popov, I. Ahmed, R. E. Hewitt, L. Franslau, P. Tyagi and L. Fruk, Nanoscale Horiz., 2023, 8, 1588 DOI: 10.1039/D3NH00269A

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