caa a22 4500 445311886 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s11095-011-0436-3 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0436-3 String-Like Micellar Nanoparticles Formed by Complexation of PEG- b -PPA and Plasmid DNA and Their Transfection Efficiency [Elektronische Daten] [Xuan Jiang, Derek Leong, Yong Ren, Zhiping Li, Michael Torbenson, Hai-Quan Mao] ABSTRACT: Purpose: To investigate the gene delivery efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver after intravenous injection and intrabiliary infusion. Methods: PEG-b-PPA/DNA micellar nanoparticles were prepared in aqueous solution through spontaneous self-assembly between plasmid DNA and PEG10K-b-PPA4K or PEG10K-b-PP13K polymer. The stability of these micellar nanoparticles in different physiological media was evaluated by monitoring the particle size change of micellar nanoparticles with dynamic light scattering (DLS). The transfection efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver was examined and compared with that of PPA/DNA nanoparticles after intravenous and intrabiliary infusion. Results: These PEG-b-PPA/DNA micellar nanoparticles exhibited unique string-like morphology under TEM. The stability of these string-like nanoparticles in salt-, serum- or bile- containing media was significantly improved compared with PPA/DNA nanoparticles. More importantly, these PEG-b-PPA/DNA nanoparticles mediated 10-fold higher transfection efficiency than PPA/DNA nanoparticles in rat liver when delivered via intrabiliary infusion. In addition, histopathological data revealed that the PEG-b-PPA/DNA nanoparticles induced minimal level of liver toxicity or damage. Conclusions: These string-like PEG-b-PPA/DNA micelles can mediate efficient transgene expression in the liver after bile duct infusion, and they have great potential to be used as effective gene carriers for liver-targeted gene delivery. Springer Science+Business Media, LLC, 2011 block copolymer nationallicence DNA micellar nanoparticles nationallicence liver-targeted gene delivery nationallicence morphology nationallicence string-like nationallicence PEG : polyethylene glycol nationallicence PPA : polyphosphoramidate nationallicence RII : retrograde intrabiliary infusion nationallicence TIBA : triisobutylaluminum nationallicence Jiang Xuan Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 205 Maryland Hall, 3400 North Charles Street, 21218, Baltimore, Maryland, USA aut Leong Derek Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 205 Maryland Hall, 3400 North Charles Street, 21218, Baltimore, Maryland, USA aut Ren Yong Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 205 Maryland Hall, 3400 North Charles Street, 21218, Baltimore, Maryland, USA aut Li Zhiping Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, 21231, Baltimore, Maryland, USA aut Torbenson Michael Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, 21231, Baltimore, Maryland, USA aut Mao Hai-Quan Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 205 Maryland Hall, 3400 North Charles Street, 21218, Baltimore, Maryland, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/6(2011-06-01), 1317-1327 0724-8741 28:6<1317 2011 28 11095 https://doi.org/10.1007/s11095-011-0436-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0436-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jiang Xuan Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 205 Maryland Hall, 3400 North Charles Street, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Leong Derek Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 205 Maryland Hall, 3400 North Charles Street, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Ren Yong Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 205 Maryland Hall, 3400 North Charles Street, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Li Zhiping Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, 21231, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Torbenson Michael Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, 21231, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Mao Hai-Quan Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 205 Maryland Hall, 3400 North Charles Street, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/6(2011-06-01), 1317-1327 0724-8741 28:6<1317 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer