title: High gene delivery efficiency of alkylated low-molecular-weight polyethylenimine through gemini surfactant-like effect.
abstract: To our knowledge, the mechanism underlying the high transfection efficiency of alkylated low-molecular-weight polyethylenimine (PEI) is not yet well understood. In this work, we grafted branched PEI (molecular weight of 1,800 Da; bPEI1800) with lauryl chains (C₁₂), and found that bPEI1800-C₁₂ was structurally similar to gemini surfactant and could similarly assemble into micelle-like particles. Stability, cellular uptake, and lysosome escape ability of bPEI1800-C₁₂/DNA polyplexes were all greatly enhanced after C₁₂ grafting. bPEI1800-C₁₂/DNA polyplexes exhibited significantly higher transfection efficiency than Lipofectamine 2000 in the presence of serum. Bioluminescence imaging showed that systemic injection of bPEI1800-C₁₂/DNA polyplexes resulted in intensive luciferase expression in vivo and bioluminescence signals that could be detected even in the head. Altogether, the high transfection efficacy of bPEI1800-C₁₂ was because bPEI1800-C₁₂, being an analog of gemini surfactant, facilitated lysosome escape and induced the coil-globule transition of DNA to assemble into a highly organized micelle-like structure that showed high stability.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China ; Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China ; Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China ; Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Ming-Ji
authors.initials: MJ
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China ; Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Wang
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, Beijing, People's Republic of China.
authors.forename: Gan-Lin
authors.initials: GL
authors.lastname: Zhang
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China ; Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shao
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China ; Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Zhong-Gao
authors.initials: ZG
authors.lastname: Gao
mesh_terms: D000478:Alkylation; D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000493:pharmacokinetics*; D004912:Erythrocytes; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D008163:Luminescent Measurements; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D011094:Polyethyleneimine / Q000737:chemistry* / Q000633:toxicity; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D013501:Surface-Active Agents / Q000737:chemistry / Q000633:toxicity; D014162:Transfection / Q000379:methods*
chemical_list: D008823:Micelles; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; D011094:Polyethyleneimine; D004247:DNA
keywords: alkylation; bioluminescence imaging; luciferase; self-organization
references.citation: Drug Deliv Transl Res. 2011 Feb 1;1(1):25-33
references.pmid: 22916337
references.citation: Angew Chem Int Ed Engl. 2003 Apr 4;42(13):1448-57
references.pmid: 12698476
references.citation: J Control Release. 2009 Oct 15;139(2):88-93
references.pmid: 19580830
references.citation: Biomaterials. 2013 Jul;34(22):5689-99
references.pmid: 23632321
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14640-5
references.pmid: 12403826
references.citation: Eur J Pharm Biopharm. 2011 Apr;77(3):438-49
references.pmid: 21093588
references.citation: Int J Pharm. 2009 Aug 13;378(1-2):201-10
references.pmid: 19501146
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5679-84
references.pmid: 15824322
references.citation: J Biomed Mater Res. 2000 Sep 5;51(3):321-8
references.pmid: 10880073
references.citation: Expert Rev Med Devices. 2011 Mar;8(2):173-85
references.pmid: 21381910
references.citation: J Phys Chem B. 2009 Aug 13;113(32):11076-84
references.pmid: 19610619
references.citation: Mol Pharm. 2009 May-Jun;6(3):727-37
references.pmid: 19178144
references.citation: J Control Release. 2007 Apr 23;118(3):357-63
references.pmid: 17313987
references.citation: ACS Nano. 2011 Sep 27;5(9):7034-47
references.pmid: 21838301
references.citation: Biomaterials. 2012 May;33(15):3942-51
references.pmid: 22365809
references.citation: Cancer Lett. 2008 Mar 18;261(2):215-25
references.pmid: 18164806
references.citation: Bioorg Med Chem. 2007 Feb 1;15(3):1504-15
references.pmid: 17113300
references.citation: PLoS One. 2011;6(9):e24438
references.pmid: 21949717
references.citation: Bioconjug Chem. 2009 Nov;20(11):2055-61
references.pmid: 19835410
references.citation: Science. 2004 Jan 30;303(5658):626-8; author reply 626-8
references.pmid: 14752144
references.citation: Nucleic Acid Ther. 2011 Jun;21(3):133-47
references.pmid: 21749290
references.citation: J Pharm Pharm Sci. 2012;15(4):548-67
references.pmid: 23106958
references.citation: J Gene Med. 2001 Mar-Apr;3(2):135-44
references.pmid: 11318112
references.citation: Nanomedicine. 2014 Feb;10(2):411-9
references.pmid: 23928214
references.citation: Expert Rev Med Devices. 2010 Jul;7(4):529-39
references.pmid: 20583889
references.citation: Chem Phys Lipids. 2001 May;111(1):59-71
references.pmid: 11438284
references.citation: Nanomedicine (Lond). 2012 Jan;7(1):65-78
references.pmid: 22191778
references.citation: Pharm Res. 2007 Jun;24(6):1079-87
references.pmid: 17387605
references.citation: J Control Release. 2010 Feb 15;141(3):339-46
references.pmid: 19836427
references.citation: J Control Release. 2010 Aug 3;145(3):182-95
references.pmid: 20226220
references.citation: J Control Release. 2009 Jan 19;133(2):132-8
references.pmid: 18929605
references.citation: J Control Release. 2008 Dec 18;132(3):236-42
references.pmid: 18597881
references.citation: Mol Pharm. 2009 Jul-Aug;6(4):1246-60
references.pmid: 19606864
references.citation: Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1203-9
references.pmid: 20381448
references.citation: J Control Release. 2010 May 10;143(3):318-25
references.pmid: 20096318
references.citation: Drug Discov Today. 2002 Oct 1;7(19):998-1001
references.pmid: 12546917