caa a22 4500 445312300 CHVBK 20180317142634.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s11095-011-0408-7 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0408-7 Enhanced Stability and Knockdown Efficiency of Poly(ethylene glycol)- b -polyphosphoramidate/siRNA Micellar Nanoparticles by Co-condensation with Sodium Triphosphate [Elektronische Daten] [Masataka Nakanishi, Rajesh Patil, Yong Ren, Rishab Shyam, Philip Wong, Hai-Quan Mao] ABSTRACT: Purpose: Polyelectrolyte complex nanoparticles are a promising vehicle for siRNA delivery but suffer from low stability under physiological conditions. An effective stabilization method is essential for the success of polycationic nanoparticle-mediated siRNA delivery. In this study, sodium triphosphate (TPP), an ionic crosslinking agent, is used to stabilize siRNA-containing nanoparticles by co-condensation. Methods: siRNA and TPP were co-encapsulated into a block copolymer, poly(ethylene glycol)-b-polyphosphoramidate (PEG-b-PPA), to form ternary nanoparticles. Physicochemical characterization was performed by dynamic light scattering and gel electrophoresis. Gene silencing efficiency in cell lines was assessed by dual luciferase assay system. Results: The PEG-b-PPA/siRNA/TPP ternary nanoparticles exhibited high uniformity with smaller size (80-100nm) compared with PEG-b-PPA/siRNA nanoparticles and showed increased stability in physiological ionic strength and serum-containing medium, due to the stabilization effect from ionic crosslinks between negatively charged TPP and cationic PPA segment. Transfection and gene silencing efficiency of the TPP-crosslinked nanoparticles were markedly improved over PEG-b-PPA/siRNA complexes in serum-containing medium. No significant difference in cell viability was observed between nanoparticles prepared with and without TPP co-condensation. Conclusions: These results demonstrated the effectiveness of TPP co-condensation in compacting polycation/siRNA nanoparticles, improving nanoparticle stability and enhancing the transfection and knockdown efficiency in serum-containing medium. Springer Science+Business Media, LLC, 2011 block copolymer gene carrier nationallicence siRNA nationallicence sodium triphosphate nationallicence stabilization nationallicence ternary nanoparticles nationallicence Nakanishi Masataka Department of Materials Science and Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut Patil Rajesh Department of Materials Science and Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut Ren Yong Department of Materials Science and Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut Shyam Rishab Department of Biomedical Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut Wong Philip Department of Neuroscience, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut Mao Hai-Quan Department of Materials Science and Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1723-1732 0724-8741 28:7<1723 2011 28 11095 https://doi.org/10.1007/s11095-011-0408-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0408-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nakanishi Masataka Department of Materials Science and Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Patil Rajesh Department of Materials Science and Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Ren Yong Department of Materials Science and Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Shyam Rishab Department of Biomedical Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Wong Philip Department of Neuroscience, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Mao Hai-Quan Department of Materials Science and Engineering, Johns Hopkins University, 21218, Baltimore, Maryland, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1723-1732 0724-8741 28:7<1723 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer