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Enhanced Gene Delivery by Palmitic Acid-Conjugated Low Molecular Weight Polyethylenimine
이두환,김원종,Kaushik Singha,박주희,조성봉 한국고분자학회 2012 Macromolecular Research Vol.20 No.3
Palmitic acid-conjugated low molecular weight polyethylenimine (PEI-g-PEG-PA) was successfully synthesized to develop an efficient non-viral gene carrier. The judicious integration of hydrophobic palmitic acid and polyethylenimine via hydrophilic polyethylene glycol (PEG) facilitated the formation of nano-sized complex (nanoplex) with plasmid DNA (pDNA) which provided the protection of pDNA against the serumic enzymatic degradation. Furthermore, the delivery system demonstrated enhanced gene transfection efficiency in comparison to unmodified low molecular weight PEI without inducing any significant cytotoxicity.
Chitosan: a novel platform in proton-driven DNA strand rearrangement actuation
Lee, Dami,Singha, Kaushik,Jang, Mi-Kyeong,Nah, Jae-Woon,Park, In-Kyu,Kim, Won Jong Royal Society of Chemistry 2009 Molecular bioSystems Vol.5 No.4
<P>Nanometre-scaled DNA machine based on molecular recognition properties of DNA has now become a powerful tool in nanodevices, miniaturized structure, and nanofabrication. The common principle behind designing a DNA nanomachine is DNA strand exchange or rearrangement, which is solely controlled by the stabilization through associative and dissociative forces arising from base pair interaction of DNA molecules. Thus, highly effective DNA reaction actuator will make DNA nanomachine more flexible, controllable, and powerful device. Here, we report the novel polymer-mediated platform in proton-driven DNA strand rearrangement actuation. This cationic low molecular weight water-soluble chitosan (LMWSC) exhibited pH-dependent complexation with oligodeoxynucleotides (ODN). It formed complex with ODN only at low pH and accelerated the DNA strand exchange (or rearrangement) reaction between dsDNA and its complementary ssDNA at pH 5.0. However, no complexation was observed between LMWSC and ODN at neutral pH. We assume that at physiological pH, LMWSC is not protonated enough for formation of complex with ODN. Therefore, it can not diminish the electrostatic repulsion among the negatively charged DNA strands of the three-stranded intermediate formed during the strand exchange reaction. In contrast, LMWSC becomes positively charged at acidic pH, and it stabilizes the three-stranded intermediate by spreading out the accumulated counter-ions and increasing the entropy of the system. This fascinating observation prompted us to believe that this intelligent proton-driven DNA reaction actuator has a potential for the precise control of DNA nanomachine and would be applied for operating and controlling nanoscaled machine.</P> <P>Graphic Abstract</P><P>Low molecular weight water-soluble chitosan (LMWSC), a pH-responsive cationic polymer, controlled the on–off of the DNA strand exchange reaction, which is a common principle behind DNA nanomachines. LMWSC operates the DNA strand exchange reaction by stabilizing the reaction intermediate only at low pH but not at neutral pH. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b818982j'> </P>