Issue 2, 2020

Star polymers with acid-labile diacetal-based cores synthesized by aqueous RAFT polymerization for intracellular DNA delivery

Abstract

The application of DNA-based therapeutics holds much potential, but it is limited by the ability to successfully deliver and transfect target cells. Here, acid-labile diacetal-based star polymers were synthesized by a facile ‘arm-first’ heterogeneous reversible addition–fragmentation chain transfer polymerization in biologically compatible solvents, for use as DNA delivery vehicles. Their cytotoxicity, DNA binding and transfection rates were evaluated. The star polymer arms are based on the biocompatible oligo(ethylene glycol) methacrylate (OEGMA) monomer, the cationic 2-(dimethylamino)ethyl methacrylate (DMAEMA) monomer and their mixtures. Their cores were prepared by the acid-labile diacetal bis[(2-methacryloyloxy)ethoxymethyl] ether (MOEME) or the non-degradable ethylene glycol dimethacrylate (EGDMA) cross-linker, for comparison. The MOEME-based star polymers showed accelerated degradation in acidic conditions. The fully cationic star polymers, PDMAEMA26-MOEME4-star and PDMAEMA26-EGDMA6-star, showed higher cytotoxicity but also considerably better DNA complexation. The higher transfection efficiency obtained for PDMAEMA26-MOEME4-star (65.5%) compared to PDMAEMA26-EGDMA6-star (44.2%) can be attributed to the ability of the former to disassemble at endosomal pH, due to its acid-labile MOEME-based core. The ability of the star polymer–DNA complexes to escape the endo/lysosomal pathway was shown to be a key determinant of transfection efficiency, as assessed by confocal microscopy and flow cytometry. In conclusion, these star polymers show promise as biocompatible, pH-labile polymers for DNA delivery that can be synthesized without the need of toxic organic solvents.

Graphical abstract: Star polymers with acid-labile diacetal-based cores synthesized by aqueous RAFT polymerization for intracellular DNA delivery

Supplementary files

Article information

Article type
Paper
Submitted
17 apr 2019
Accepted
27 jún 2019
First published
05 júl 2019

Polym. Chem., 2020,11, 344-357

Star polymers with acid-labile diacetal-based cores synthesized by aqueous RAFT polymerization for intracellular DNA delivery

T. J. Gibson, P. Smyth, M. Semsarilar, A. P. McCann, W. J. McDaid, M. C. Johnston, C. J. Scott and E. Themistou, Polym. Chem., 2020, 11, 344 DOI: 10.1039/C9PY00573K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements