Issue 28, 2024

Advancing nucleic acid delivery through cationic polymer design: non-cationic building blocks from the toolbox

Abstract

Polymers used for the delivery of nucleic acids (NAs) typically possess ionizable, cationic moieties enabling their electrostatic interactions with negatively charged NAs and form stable polyplexes. However, non-cationic building blocks have been harnessed to design cationic polymers with enhanced delivery of DNA/RNA to tissues, cells, and subcellular compartments while remaining stable in biological fluids. By customizing the chemistry of these functional groups, we can improve cell targeting behavior, uptake, endosomal escape, non-toxicity, and transfection efficiency. Additionally, the physicochemical properties, such as the loading capacity, complexation ability, size and morphology, biodegradability, pH sensitivity, and amphiphilicity, can be adjusted based on the specific application. This review summarizes the role of non-cationic moieties in various biomedical contexts, from therapeutic interventions to gene editing. By unpacking and critically summarizing the existing literature, this review provides valuable insights into the rational integration of these building blocks for designing more effective nanovectors to deliver NAs.

Graphical abstract: Advancing nucleic acid delivery through cationic polymer design: non-cationic building blocks from the toolbox

Article information

Article type
Review Article
Submitted
01 Mar 2024
Accepted
22 Jun 2024
First published
24 Jun 2024
This article is Open Access
Creative Commons BY license

Polym. Chem., 2024,15, 2800-2826

Advancing nucleic acid delivery through cationic polymer design: non-cationic building blocks from the toolbox

I. Porello, N. Bono, G. Candiani and F. Cellesi, Polym. Chem., 2024, 15, 2800 DOI: 10.1039/D4PY00234B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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