title: Self-catalyzed degradable cationic polymer for release of DNA.
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.
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, Australia.
authors.forename: Nghia P
authors.initials: NP
authors.lastname: Truong
authors.forename: Zhongfan
authors.initials: Z
authors.lastname: Jia
authors.forename: Melinda
authors.initials: M
authors.lastname: Burgess
authors.forename: Liz
authors.initials: L
authors.lastname: Payne
authors.forename: Nigel A J
authors.initials: NA
authors.lastname: McMillan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Monteiro
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002384:Catalysis; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D018716:Molecular Mimicry; D053758:Nanoparticles; D009838:Oligodeoxyribonucleotides / Q000378:metabolism* / Q000494:pharmacology; D010316:Particle Size; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; D002412:Cations; D003692:Delayed-Action Preparations; D009838:Oligodeoxyribonucleotides; D034741:RNA, Small Interfering; C006903:carbopol 940