Self-catalyzed degradable cationic polymer for release of DNA

Nghia Truong Phuoc, Zhongfan Jia, Melinda Burgess, Elizabeth Payne, Nigel Alan John McMillan, Michael J Monteiro

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48 Citations (Scopus)

Abstract

The controlled release of siRNA or DNA complexes from cationic polymers is an important parameter design in polymer-based delivery carriers. In this work, we use the self-catalyzed degradable poly(2-dimethylaminoethyl acrylate) (PDMAEA) to strongly bind, protect, and then release oligo DNA (a mimic for siRNA) without the need for a cellular or external trigger. This self-catalyzed hydrolysis process of PDMAEA forms poly(acrylic acid) and N,N -dimethylamino ethyl ethanol, both of which have little or no toxicity to cells, and offers the advantage of little or no toxicity to off-target cells and tissues. We found that PDMAEA makes an ideal component of a delivery carrier by protecting the oligo DNA for a sufficiently long period of time to transfect most cells (80 transfection after 4 h) and then has the capacity to release the DNA inside the cells after 10 h. The PDMAEA formed large nanoparticle complexes with oligo DNA of 400 nm that protected the oligo DNA from DNase in serum. The nanoparticle complexes showed no toxicity for all molecular weights at a nitrogen/phosphorus (N/P) ratio of 10. Only the higher molecular weight polymers at very high N/P ratios of 200 showed significant levels of cytotoxicity. These attributes make PDMAEA a promising candidate as a component in the design of a gene delivery carrier without the concern about accumulated toxicity of nanoparticles in the human body after multiadministration, an issue that has become increasingly more important.
Original languageEnglish
Pages (from-to)3540 - 3548
Number of pages9
JournalBiomacromolecules
Volume12
Issue number10
DOIs
Publication statusPublished - 2011
Externally publishedYes

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