The Impact of Nylon-3 Copolymer Composition on the Efficiency of siRNA Delivery to Glioblastoma Cells
Identifieur interne : 000729 ( Pmc/Curation ); précédent : 000728; suivant : 000730The Impact of Nylon-3 Copolymer Composition on the Efficiency of siRNA Delivery to Glioblastoma Cells
Auteurs : Natascha Hartl [Allemagne] ; Friederike Adams [Allemagne] ; Gabriella Costabile [Allemagne] ; Lorenz Isert [Allemagne] ; Markus Döblinger [Allemagne] ; Ximian Xiao [République populaire de Chine] ; Runhui Liu [République populaire de Chine] ; Olivia M. Merkel [Allemagne]Source :
- Nanomaterials [ 2079-4991 ] ; 2019.
Abstract
Glioblastoma multiforme is a devastating disease that has attracted enormous attention due to poor prognosis and high recurrence. Small interfering RNA (siRNA) in principle offers a promising therapeutic approach by the downregulation of disease-related genes via RNA interference. For efficient siRNA delivery to target sites, cationic polymers are often used in preclinical studies for the protection of siRNA and complex formation based on electrostatic interactions. In an effort to develop biocompatible and efficient nanocarriers with a translational outlook for optimal gene silencing at reduced toxicity, we synthesized two sets of nylon-3 copolymers with variable cationic content (DM or NM monomer) and hydrophobic subunits (CP monomer) and evaluated their suitability for in vitro siRNA delivery into glioblastoma cells. DM0.4/CP0.6 and NM0.4/CP0.6 polymers with similar subunit ratios were synthesized to compare the effect of different cationic subunits. Additionally, we utilized NM0.2/CP0.8 polymers to evaluate the impact of the different hydrophobic content in the polymer chain. The siRNA condensation ability and polymer–siRNA complex stability was evaluated by unmodified and modified SYBR gold assays, respectively. Further physicochemical characteristics, e.g., particle size and surface charge, were evaluated by dynamic light scattering and laser Doppler anemometry, whereas a relatively new method for polyplex size distribution analysis—tunable resistive pulse sensing—was additionally developed and compared to DLS measurements. Transfection efficiencies, the route of cell internalization, and protein knockdown abilities in glioblastoma cells were investigated by flow cytometry. Furthermore, cellular tolerability was evaluated by MTT and LDH assays. All the polymers efficiently condensed siRNA at N/P ratios of three, whereas polymers with NM cationic subunits demonstrated smaller particle size and lower polyplex stability. Furthermore, NM0.2/CP0.8 polyplexes with the highest hydrophobic content displayed significantly higher cellular internalization in comparison to more cationic formulations and successful knockdown capabilities. Detailed investigations of the cellular uptake route demonstrated that these polyplexes mainly follow clathrin-mediated endocytotic uptake mechanisms, implying high interaction capacity with cellular membranes. Taken together with conducive toxicity profiles, highly hydrophobic nylon-3 polymers provide an appropriate siRNA delivery agent for the potential treatment of glioblastoma.
Url:
DOI: 10.3390/nano9070986
PubMed: 31288448
PubMed Central: 6669510
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<series><title level="j">Nanomaterials</title>
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<front><div type="abstract" xml:lang="en"><p>Glioblastoma multiforme is a devastating disease that has attracted enormous attention due to poor prognosis and high recurrence. Small interfering RNA (siRNA) in principle offers a promising therapeutic approach by the downregulation of disease-related genes via RNA interference. For efficient siRNA delivery to target sites, cationic polymers are often used in preclinical studies for the protection of siRNA and complex formation based on electrostatic interactions. In an effort to develop biocompatible and efficient nanocarriers with a translational outlook for optimal gene silencing at reduced toxicity, we synthesized two sets of nylon-3 copolymers with variable cationic content (DM or NM monomer) and hydrophobic subunits (CP monomer) and evaluated their suitability for in vitro siRNA delivery into glioblastoma cells. DM<sub>0.4</sub>
/CP<sub>0.6</sub>
and NM<sub>0.4</sub>
/CP<sub>0.6</sub>
polymers with similar subunit ratios were synthesized to compare the effect of different cationic subunits. Additionally, we utilized NM<sub>0.2</sub>
/CP<sub>0.8</sub>
polymers to evaluate the impact of the different hydrophobic content in the polymer chain. The siRNA condensation ability and polymer–siRNA complex stability was evaluated by unmodified and modified SYBR gold assays, respectively. Further physicochemical characteristics, e.g., particle size and surface charge, were evaluated by dynamic light scattering and laser Doppler anemometry, whereas a relatively new method for polyplex size distribution analysis—tunable resistive pulse sensing—was additionally developed and compared to DLS measurements. Transfection efficiencies, the route of cell internalization, and protein knockdown abilities in glioblastoma cells were investigated by flow cytometry. Furthermore, cellular tolerability was evaluated by MTT and LDH assays. All the polymers efficiently condensed siRNA at N/P ratios of three, whereas polymers with NM cationic subunits demonstrated smaller particle size and lower polyplex stability. Furthermore, NM<sub>0.2</sub>
/CP<sub>0.8</sub>
polyplexes with the highest hydrophobic content displayed significantly higher cellular internalization in comparison to more cationic formulations and successful knockdown capabilities. Detailed investigations of the cellular uptake route demonstrated that these polyplexes mainly follow clathrin-mediated endocytotic uptake mechanisms, implying high interaction capacity with cellular membranes. Taken together with conducive toxicity profiles, highly hydrophobic nylon-3 polymers provide an appropriate siRNA delivery agent for the potential treatment of glioblastoma.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hottinger, A F" uniqKey="Hottinger A">A.F. Hottinger</name>
</author>
<author><name sortKey="Stupp, R" uniqKey="Stupp R">R. Stupp</name>
</author>
<author><name sortKey="Homicsko, K" uniqKey="Homicsko K">K. Homicsko</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thakkar, J P" uniqKey="Thakkar J">J.P. Thakkar</name>
</author>
<author><name sortKey="Dolecek, T" uniqKey="Dolecek T">T. Dolecek</name>
</author>
<author><name sortKey="Horbinski, T A" uniqKey="Horbinski T">T.A. Horbinski</name>
</author>
<author><name sortKey="Ostrom, Q T" uniqKey="Ostrom Q">Q.T. Ostrom</name>
</author>
<author><name sortKey="Lightner, D D" uniqKey="Lightner D">D.D. Lightner</name>
</author>
<author><name sortKey="Barnholtz Sloan, J S" uniqKey="Barnholtz Sloan J">J.S. Barnholtz-Sloan</name>
</author>
<author><name sortKey="Villano, J L" uniqKey="Villano J">J.L. Villano</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jinek, M" uniqKey="Jinek M">M. Jinek</name>
</author>
<author><name sortKey="Doudna, J A" uniqKey="Doudna J">J.A. Doudna</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Davis, M E" uniqKey="Davis M">M.E. Davis</name>
</author>
<author><name sortKey="Zuckermann, J E" uniqKey="Zuckermann J">J.E. Zuckermann</name>
</author>
<author><name sortKey="Choi, C H J" uniqKey="Choi C">C.H.J. Choi</name>
</author>
<author><name sortKey="Seligson, D" uniqKey="Seligson D">D. Seligson</name>
</author>
<author><name sortKey="Tolcher, A" uniqKey="Tolcher A">A. Tolcher</name>
</author>
<author><name sortKey="Alabi, A" uniqKey="Alabi A">A. Alabi</name>
</author>
<author><name sortKey="Yen, Y" uniqKey="Yen Y">Y. Yen</name>
</author>
<author><name sortKey="Heidel, J D" uniqKey="Heidel J">J.D. Heidel</name>
</author>
<author><name sortKey="Ribas, A" uniqKey="Ribas A">A. Ribas</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Coelho, T" uniqKey="Coelho T">T. Coelho</name>
</author>
<author><name sortKey="Adams, D" uniqKey="Adams D">D. Adams</name>
</author>
<author><name sortKey="Silva, A" uniqKey="Silva A">A. Silva</name>
</author>
<author><name sortKey="Lozeron, P" uniqKey="Lozeron P">P. Lozeron</name>
</author>
<author><name sortKey="Hawkins, P N" uniqKey="Hawkins P">P.N. Hawkins</name>
</author>
<author><name sortKey="Mant, T" uniqKey="Mant T">T. Mant</name>
</author>
<author><name sortKey="Perez, J" uniqKey="Perez J">J. Perez</name>
</author>
<author><name sortKey="Chiesa, J" uniqKey="Chiesa J">J. Chiesa</name>
</author>
<author><name sortKey="Warrington, S" uniqKey="Warrington S">S. Warrington</name>
</author>
<author><name sortKey="Tranter, E" uniqKey="Tranter E">E. Tranter</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zimmermann, T" uniqKey="Zimmermann T">T. Zimmermann</name>
</author>
<author><name sortKey="Karsten, V" uniqKey="Karsten V">V. Karsten</name>
</author>
<author><name sortKey="Harrop, J" uniqKey="Harrop J">J. Harrop</name>
</author>
<author><name sortKey="Chan, A" uniqKey="Chan A">A. Chan</name>
</author>
<author><name sortKey="Chiesa, J" uniqKey="Chiesa J">J. Chiesa</name>
</author>
<author><name sortKey="Peters, G" uniqKey="Peters G">G. Peters</name>
</author>
<author><name sortKey="Falzone, R" uniqKey="Falzone R">R. Falzone</name>
</author>
<author><name sortKey="Cehelsky, J" uniqKey="Cehelsky J">J. Cehelsky</name>
</author>
<author><name sortKey="Nochur, S" uniqKey="Nochur S">S. Nochur</name>
</author>
<author><name sortKey="Vaishnaw, A" uniqKey="Vaishnaw A">A. Vaishnaw</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kim, M G" uniqKey="Kim M">M.G. Kim</name>
</author>
<author><name sortKey="Jo, S D" uniqKey="Jo S">S.D. Jo</name>
</author>
<author><name sortKey="Yhee, J Y" uniqKey="Yhee J">J.Y. Yhee</name>
</author>
<author><name sortKey="Lee, B S" uniqKey="Lee B">B.S. Lee</name>
</author>
<author><name sortKey="Lee, S J" uniqKey="Lee S">S.J. Lee</name>
</author>
<author><name sortKey="Park, S G" uniqKey="Park S">S.G. Park</name>
</author>
<author><name sortKey="Kang, S W" uniqKey="Kang S">S.W. Kang</name>
</author>
<author><name sortKey="Kim, S H" uniqKey="Kim S">S.H. Kim</name>
</author>
<author><name sortKey="Jeong, J H" uniqKey="Jeong J">J.H. Jeong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Grzelinski, M" uniqKey="Grzelinski M">M. Grzelinski</name>
</author>
<author><name sortKey="Urban Klein, B" uniqKey="Urban Klein B">B. Urban-Klein</name>
</author>
<author><name sortKey="Martens, T" uniqKey="Martens T">T. Martens</name>
</author>
<author><name sortKey="Lamszus, K" uniqKey="Lamszus K">K. Lamszus</name>
</author>
<author><name sortKey="Bakowsky, U" uniqKey="Bakowsky U">U. Bakowsky</name>
</author>
<author><name sortKey="Hobel, S" uniqKey="Hobel S">S. Hobel</name>
</author>
<author><name sortKey="Czubayko, F" uniqKey="Czubayko F">F. Czubayko</name>
</author>
<author><name sortKey="Aigner, A" uniqKey="Aigner A">A. Aigner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zukiel, R" uniqKey="Zukiel R">R. Zukiel</name>
</author>
<author><name sortKey="Nowak, S" uniqKey="Nowak S">S. Nowak</name>
</author>
<author><name sortKey="Wyszko, E" uniqKey="Wyszko E">E. Wyszko</name>
</author>
<author><name sortKey="Rolle, K" uniqKey="Rolle K">K. Rolle</name>
</author>
<author><name sortKey="Gawronska, I" uniqKey="Gawronska I">I. Gawronska</name>
</author>
<author><name sortKey="Barciszewska, M Z" uniqKey="Barciszewska M">M.Z. Barciszewska</name>
</author>
<author><name sortKey="Barciszewski, J" uniqKey="Barciszewski J">J. Barciszewski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bruun, J" uniqKey="Bruun J">J. Bruun</name>
</author>
<author><name sortKey="Larsen, T B" uniqKey="Larsen T">T.B. Larsen</name>
</author>
<author><name sortKey="J Lck, R I" uniqKey="J Lck R">R.I. Jølck</name>
</author>
<author><name sortKey="Eliasen, R" uniqKey="Eliasen R">R. Eliasen</name>
</author>
<author><name sortKey="Holm, R" uniqKey="Holm R">R. Holm</name>
</author>
<author><name sortKey="Gjetting, T" uniqKey="Gjetting T">T. Gjetting</name>
</author>
<author><name sortKey="Andresen, T L" uniqKey="Andresen T">T.L. Andresen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Qiu, J" uniqKey="Qiu J">J. Qiu</name>
</author>
<author><name sortKey="Kong, L" uniqKey="Kong L">L. Kong</name>
</author>
<author><name sortKey="Cao, X" uniqKey="Cao X">X. Cao</name>
</author>
<author><name sortKey="Li, A" uniqKey="Li A">A. Li</name>
</author>
<author><name sortKey="Wei, P" uniqKey="Wei P">P. Wei</name>
</author>
<author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name>
</author>
<author><name sortKey="Mignani, S" uniqKey="Mignani S">S. Mignani</name>
</author>
<author><name sortKey="Caminade, A M" uniqKey="Caminade A">A.-M. Caminade</name>
</author>
<author><name sortKey="Majoral, J P" uniqKey="Majoral J">J.-P. Majoral</name>
</author>
<author><name sortKey="Shi, X" uniqKey="Shi X">X. Shi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kong, L" uniqKey="Kong L">L. Kong</name>
</author>
<author><name sortKey="Qiu, J" uniqKey="Qiu J">J. Qiu</name>
</author>
<author><name sortKey="Sun, W" uniqKey="Sun W">W. Sun</name>
</author>
<author><name sortKey="Yang, J" uniqKey="Yang J">J. Yang</name>
</author>
<author><name sortKey="Shen, M" uniqKey="Shen M">M. Shen</name>
</author>
<author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name>
</author>
<author><name sortKey="Shi, X" uniqKey="Shi X">X. Shi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wan, Y" uniqKey="Wan Y">Y. Wan</name>
</author>
<author><name sortKey="Moyle, P M" uniqKey="Moyle P">P.M. Moyle</name>
</author>
<author><name sortKey="Christie, M P" uniqKey="Christie M">M.P. Christie</name>
</author>
<author><name sortKey="Toth, I" uniqKey="Toth I">I. Toth</name>
</author>
<author><name sortKey="Wan, Y" uniqKey="Wan Y">Y. Wan</name>
</author>
<author><name sortKey="Moyle, P M" uniqKey="Moyle P">P.M. Moyle</name>
</author>
<author><name sortKey="Christie, P M" uniqKey="Christie P">P.M. Christie</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rettig, G R" uniqKey="Rettig G">G.R. Rettig</name>
</author>
<author><name sortKey="Behlke, M A" uniqKey="Behlke M">M.A. Behlke</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Moghimi, S M" uniqKey="Moghimi S">S.M. Moghimi</name>
</author>
<author><name sortKey="Symonds, P" uniqKey="Symonds P">P. Symonds</name>
</author>
<author><name sortKey="Murray, J C" uniqKey="Murray J">J.C. Murray</name>
</author>
<author><name sortKey="Hunter, A C" uniqKey="Hunter A">A.C. Hunter</name>
</author>
<author><name sortKey="Debska, G" uniqKey="Debska G">G. Debska</name>
</author>
<author><name sortKey="Szewczyk, A" uniqKey="Szewczyk A">A. Szewczyk</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Navarro, G" uniqKey="Navarro G">G. Navarro</name>
</author>
<author><name sortKey="Essex, S" uniqKey="Essex S">S. Essex</name>
</author>
<author><name sortKey="Sawant, R R" uniqKey="Sawant R">R.R. Sawant</name>
</author>
<author><name sortKey="Biswas, S" uniqKey="Biswas S">S. Biswas</name>
</author>
<author><name sortKey="Nagesha, D" uniqKey="Nagesha D">D. Nagesha</name>
</author>
<author><name sortKey="Sridhar, S" uniqKey="Sridhar S">S. Sridhar</name>
</author>
<author><name sortKey="De Ilarduya, C T" uniqKey="De Ilarduya C">C.T. de ILarduya</name>
</author>
<author><name sortKey="Torchilin, V P" uniqKey="Torchilin V">V.P. Torchilin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bielinska, A" uniqKey="Bielinska A">A. Bielinska</name>
</author>
<author><name sortKey="Kukowska Latallo, J F" uniqKey="Kukowska Latallo J">J.F. Kukowska-Latallo</name>
</author>
<author><name sortKey="Johnson, J" uniqKey="Johnson J">J. Johnson</name>
</author>
<author><name sortKey="Tomalia, D A" uniqKey="Tomalia D">D.A. Tomalia</name>
</author>
<author><name sortKey="Baker, J R" uniqKey="Baker J">J.R. Baker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, L" uniqKey="Liu L">L. Liu</name>
</author>
<author><name sortKey="Zheng, M" uniqKey="Zheng M">M. Zheng</name>
</author>
<author><name sortKey="Librizzi, D" uniqKey="Librizzi D">D. Librizzi</name>
</author>
<author><name sortKey="Renette, T" uniqKey="Renette T">T. Renette</name>
</author>
<author><name sortKey="Merkel, O M" uniqKey="Merkel O">O.M. Merkel</name>
</author>
<author><name sortKey="Kissel, T" uniqKey="Kissel T">T. Kissel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Navarro, G" uniqKey="Navarro G">G. Navarro</name>
</author>
<author><name sortKey="Pan, J" uniqKey="Pan J">J. Pan</name>
</author>
<author><name sortKey="Torchilin, V P" uniqKey="Torchilin V">V.P. Torchilin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mowery, B P" uniqKey="Mowery B">B.P. Mowery</name>
</author>
<author><name sortKey="Lee, S E" uniqKey="Lee S">S.E. Lee</name>
</author>
<author><name sortKey="Kissounko, D A" uniqKey="Kissounko D">D.A. Kissounko</name>
</author>
<author><name sortKey="Epand, R F" uniqKey="Epand R">R.F. Epand</name>
</author>
<author><name sortKey="Epand, R M" uniqKey="Epand R">R.M. Epand</name>
</author>
<author><name sortKey="Weisblum, B" uniqKey="Weisblum B">B. Weisblum</name>
</author>
<author><name sortKey="Stahl, S S" uniqKey="Stahl S">S.S. Stahl</name>
</author>
<author><name sortKey="Gellman, S H" uniqKey="Gellman S">S.H. Gellman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dohm, M T" uniqKey="Dohm M">M.T. Dohm</name>
</author>
<author><name sortKey="Mowery, B P" uniqKey="Mowery B">B.P. Mowery</name>
</author>
<author><name sortKey="Czyzewski, A M" uniqKey="Czyzewski A">A.M. Czyzewski</name>
</author>
<author><name sortKey="Stahl, S S" uniqKey="Stahl S">S.S. Stahl</name>
</author>
<author><name sortKey="Gellman, S H" uniqKey="Gellman S">S.H. Gellman</name>
</author>
<author><name sortKey="Barron, A E" uniqKey="Barron A">A.E. Barron</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dane, E L" uniqKey="Dane E">E.L. Dane</name>
</author>
<author><name sortKey="Grinstaff, M W" uniqKey="Grinstaff M">M.W. Grinstaff</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lee, M R" uniqKey="Lee M">M.R. Lee</name>
</author>
<author><name sortKey="Stahl, S S" uniqKey="Stahl S">S.S. Stahl</name>
</author>
<author><name sortKey="Gellman, S H" uniqKey="Gellman S">S.H. Gellman</name>
</author>
<author><name sortKey="Masters, K S" uniqKey="Masters K">K.S. Masters</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nadithe, V" uniqKey="Nadithe V">V. Nadithe</name>
</author>
<author><name sortKey="Liu, R" uniqKey="Liu R">R. Liu</name>
</author>
<author><name sortKey="Killinger, B A" uniqKey="Killinger B">B.A. Killinger</name>
</author>
<author><name sortKey="Movassaghian, S" uniqKey="Movassaghian S">S. Movassaghian</name>
</author>
<author><name sortKey="Kim, N H" uniqKey="Kim N">N.H. Kim</name>
</author>
<author><name sortKey="Moszczynska, A B" uniqKey="Moszczynska A">A.B. Moszczynska</name>
</author>
<author><name sortKey="Masters, K S" uniqKey="Masters K">K.S. Masters</name>
</author>
<author><name sortKey="Gellman, S H" uniqKey="Gellman S">S.H. Gellman</name>
</author>
<author><name sortKey="Merkel, O M" uniqKey="Merkel O">O.M. Merkel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, R" uniqKey="Liu R">R. Liu</name>
</author>
<author><name sortKey="Masters, K S" uniqKey="Masters K">K.S. Masters</name>
</author>
<author><name sortKey="Gellman, S H" uniqKey="Gellman S">S.H. Gellman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, R" uniqKey="Liu R">R. Liu</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X. Chen</name>
</author>
<author><name sortKey="Hayouka, Z" uniqKey="Hayouka Z">Z. Hayouka</name>
</author>
<author><name sortKey="Chakraborty, S" uniqKey="Chakraborty S">S. Chakraborty</name>
</author>
<author><name sortKey="Falk, S P" uniqKey="Falk S">S.P. Falk</name>
</author>
<author><name sortKey="Weisblum, B" uniqKey="Weisblum B">B. Weisblum</name>
</author>
<author><name sortKey="Masters, K S" uniqKey="Masters K">K.S. Masters</name>
</author>
<author><name sortKey="Gellman, S H" uniqKey="Gellman S">S.H. Gellman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, R" uniqKey="Liu R">R. Liu</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X. Chen</name>
</author>
<author><name sortKey="Falk, S P" uniqKey="Falk S">S.P. Falk</name>
</author>
<author><name sortKey="Mowery, B P" uniqKey="Mowery B">B.P. Mowery</name>
</author>
<author><name sortKey="Karlsson, A J" uniqKey="Karlsson A">A.J. Karlsson</name>
</author>
<author><name sortKey="Weisblum, B" uniqKey="Weisblum B">B. Weisblum</name>
</author>
<author><name sortKey="Palecek, S P" uniqKey="Palecek S">S.P. Palecek</name>
</author>
<author><name sortKey="Masters, K S" uniqKey="Masters K">K.S. Masters</name>
</author>
<author><name sortKey="Gellman, S H" uniqKey="Gellman S">S.H. Gellman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name>
</author>
<author><name sortKey="Kissounko, D A" uniqKey="Kissounko D">D.A. Kissounko</name>
</author>
<author><name sortKey="Lee, S E" uniqKey="Lee S">S.E. Lee</name>
</author>
<author><name sortKey="Gellman, S H" uniqKey="Gellman S">S.H. Gellman</name>
</author>
<author><name sortKey="Stahl, S S" uniqKey="Stahl S">S.S. Stahl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Elsayed, M" uniqKey="Elsayed M">M. Elsayed</name>
</author>
<author><name sortKey="Corrand, V" uniqKey="Corrand V">V. Corrand</name>
</author>
<author><name sortKey="Kolhatkar, V" uniqKey="Kolhatkar V">V. Kolhatkar</name>
</author>
<author><name sortKey="Xie, Y" uniqKey="Xie Y">Y. Xie</name>
</author>
<author><name sortKey="Kim, N H" uniqKey="Kim N">N.H. Kim</name>
</author>
<author><name sortKey="Kolhatkar, R" uniqKey="Kolhatkar R">R. Kolhatkar</name>
</author>
<author><name sortKey="Merkel, O M" uniqKey="Merkel O">O.M. Merkel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Merkel, O M" uniqKey="Merkel O">O.M. Merkel</name>
</author>
<author><name sortKey="Librizzi, D" uniqKey="Librizzi D">D. Librizzi</name>
</author>
<author><name sortKey="Pfestroff, A" uniqKey="Pfestroff A">A. Pfestroff</name>
</author>
<author><name sortKey="Schurrat, T" uniqKey="Schurrat T">T. Schurrat</name>
</author>
<author><name sortKey="Behe, M" uniqKey="Behe M">M. Béhé</name>
</author>
<author><name sortKey="Kissel, T" uniqKey="Kissel T">T. Kissel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Benfer, M" uniqKey="Benfer M">M. Benfer</name>
</author>
<author><name sortKey="Kissel, T" uniqKey="Kissel T">T. Kissel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name>
</author>
<author><name sortKey="Peterson, D" uniqKey="Peterson D">D. Peterson</name>
</author>
<author><name sortKey="Hideo, K" uniqKey="Hideo K">K. Hideo</name>
</author>
<author><name sortKey="David, S" uniqKey="David S">S. David</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Han, X" uniqKey="Han X">X. Han</name>
</author>
<author><name sortKey="Gelein, R" uniqKey="Gelein R">R. Gelein</name>
</author>
<author><name sortKey="Corson, N" uniqKey="Corson N">N. Corson</name>
</author>
<author><name sortKey="Wade Mercer, P" uniqKey="Wade Mercer P">P. Wade-Mercer</name>
</author>
<author><name sortKey="Jiang, J" uniqKey="Jiang J">J. Jiang</name>
</author>
<author><name sortKey="Biswas, P" uniqKey="Biswas P">P. Biswas</name>
</author>
<author><name sortKey="Finkelstein, J N" uniqKey="Finkelstein J">J.N. Finkelstein</name>
</author>
<author><name sortKey="Elder, A" uniqKey="Elder A">A. Elder</name>
</author>
<author><name sortKey="Oberdorster, G" uniqKey="Oberdorster G">G. Oberdörster</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Guo, D" uniqKey="Guo D">D. Guo</name>
</author>
<author><name sortKey="Wang, B" uniqKey="Wang B">B. Wang</name>
</author>
<author><name sortKey="Han, F" uniqKey="Han F">F. Han</name>
</author>
<author><name sortKey="Lei, T" uniqKey="Lei T">T. Lei</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="De Martimprey, H" uniqKey="De Martimprey H">H. De Martimprey</name>
</author>
<author><name sortKey="Vauthier, C" uniqKey="Vauthier C">C. Vauthier</name>
</author>
<author><name sortKey="Malvy, C" uniqKey="Malvy C">C. Malvy</name>
</author>
<author><name sortKey="Couvreur, P" uniqKey="Couvreur P">P. Couvreur</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jones, S K" uniqKey="Jones S">S.K. Jones</name>
</author>
<author><name sortKey="Lizzio, V" uniqKey="Lizzio V">V. Lizzio</name>
</author>
<author><name sortKey="Merkel, O M" uniqKey="Merkel O">O.M. Merkel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Aigner, A" uniqKey="Aigner A">A. Aigner</name>
</author>
<author><name sortKey="Kogel, D" uniqKey="Kogel D">D. Kögel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zheng, M" uniqKey="Zheng M">M. Zheng</name>
</author>
<author><name sortKey="Pavan, G M" uniqKey="Pavan G">G.M. Pavan</name>
</author>
<author><name sortKey="Neeb, M" uniqKey="Neeb M">M. Neeb</name>
</author>
<author><name sortKey="Schaper, A K" uniqKey="Schaper A">A.K. Schaper</name>
</author>
<author><name sortKey="Danani, A" uniqKey="Danani A">A. Danani</name>
</author>
<author><name sortKey="Klebe, G" uniqKey="Klebe G">G. Klebe</name>
</author>
<author><name sortKey="Merkel, O M" uniqKey="Merkel O">O.M. Merkel</name>
</author>
<author><name sortKey="Kissel, T" uniqKey="Kissel T">T. Kissel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Weatherall, E" uniqKey="Weatherall E">E. Weatherall</name>
</author>
<author><name sortKey="Willmott, G R" uniqKey="Willmott G">G.R. Willmott</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kabanov, A V" uniqKey="Kabanov A">A.V. Kabanov</name>
</author>
<author><name sortKey="Kabanov, V A" uniqKey="Kabanov V">V.A. Kabanov</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rejman, J" uniqKey="Rejman J">J. Rejman</name>
</author>
<author><name sortKey="Bragonzi, A" uniqKey="Bragonzi A">A. Bragonzi</name>
</author>
<author><name sortKey="Conese, M" uniqKey="Conese M">M. Conese</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ruponen, M" uniqKey="Ruponen M">M. Ruponen</name>
</author>
<author><name sortKey="Yl Herttuala, S" uniqKey="Yl Herttuala S">S. Ylä-Herttuala</name>
</author>
<author><name sortKey="Urtti, A" uniqKey="Urtti A">A. Urtti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Samuel, J" uniqKey="Samuel J">J. Samuel</name>
</author>
<author><name sortKey="Lavasanifar, A" uniqKey="Lavasanifar A">A. Lavasanifar</name>
</author>
<author><name sortKey="Alshamsan, A" uniqKey="Alshamsan A">A. Alshamsan</name>
</author>
<author><name sortKey="Uluda, H" uniqKey="Uluda H">H. Uludağ</name>
</author>
<author><name sortKey="Haddadi, A" uniqKey="Haddadi A">A. Haddadi</name>
</author>
<author><name sortKey="Incani, V" uniqKey="Incani V">V. Incani</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Biswas, S" uniqKey="Biswas S">S. Biswas</name>
</author>
<author><name sortKey="Deshpande, P P" uniqKey="Deshpande P">P.P. Deshpande</name>
</author>
<author><name sortKey="Navarro, G" uniqKey="Navarro G">G. Navarro</name>
</author>
<author><name sortKey="Dodwadkar, N S" uniqKey="Dodwadkar N">N.S. Dodwadkar</name>
</author>
<author><name sortKey="Torchilin, V P" uniqKey="Torchilin V">V.P. Torchilin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Win, K Y" uniqKey="Win K">K.Y. Win</name>
</author>
<author><name sortKey="Feng, S" uniqKey="Feng S">S. Feng</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ivanov, A I" uniqKey="Ivanov A">A.I. Ivanov</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, L H" uniqKey="Wang L">L.H. Wang</name>
</author>
<author><name sortKey="Rothberg, K G" uniqKey="Rothberg K">K.G. Rothberg</name>
</author>
<author><name sortKey="Anderson, R G W" uniqKey="Anderson R">R.G.W. Anderson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rodal, S K" uniqKey="Rodal S">S.K. Rodal</name>
</author>
<author><name sortKey="Skretting, G" uniqKey="Skretting G">G. Skretting</name>
</author>
<author><name sortKey="Garred, O" uniqKey="Garred O">O. Garred</name>
</author>
<author><name sortKey="Vilhardt, F" uniqKey="Vilhardt F">F. Vilhardt</name>
</author>
<author><name sortKey="Van Deurs, B" uniqKey="Van Deurs B">B. van Deurs</name>
</author>
<author><name sortKey="Sandvig, K" uniqKey="Sandvig K">K. Sandvig</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lu, J J" uniqKey="Lu J">J.J. Lu</name>
</author>
<author><name sortKey="Langer, R" uniqKey="Langer R">R. Langer</name>
</author>
<author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Merkel, O M" uniqKey="Merkel O">O.M. Merkel</name>
</author>
<author><name sortKey="Librizzi, D" uniqKey="Librizzi D">D. Librizzi</name>
</author>
<author><name sortKey="Pfestroff, A" uniqKey="Pfestroff A">A. Pfestroff</name>
</author>
<author><name sortKey="Schurrat, T" uniqKey="Schurrat T">T. Schurrat</name>
</author>
<author><name sortKey="Buyens, K" uniqKey="Buyens K">K. Buyens</name>
</author>
<author><name sortKey="Sanders, N N" uniqKey="Sanders N">N.N. Sanders</name>
</author>
<author><name sortKey="De Smedt, S C" uniqKey="De Smedt S">S.C. De Smedt</name>
</author>
<author><name sortKey="Behe, M" uniqKey="Behe M">M. Béhé</name>
</author>
<author><name sortKey="Kissel, T" uniqKey="Kissel T">T. Kissel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Martens, T F" uniqKey="Martens T">T.F. Martens</name>
</author>
<author><name sortKey="Remaut, K" uniqKey="Remaut K">K. Remaut</name>
</author>
<author><name sortKey="Demeester, J" uniqKey="Demeester J">J. Demeester</name>
</author>
<author><name sortKey="De Smedt, S C" uniqKey="De Smedt S">S.C. De Smedt</name>
</author>
<author><name sortKey="Braeckmans, K" uniqKey="Braeckmans K">K. Braeckmans</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nguyen, J" uniqKey="Nguyen J">J. Nguyen</name>
</author>
<author><name sortKey="Szoka, F C" uniqKey="Szoka F">F.C. Szoka</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Merkel, O M" uniqKey="Merkel O">O.M. Merkel</name>
</author>
<author><name sortKey="Mintzer, M A" uniqKey="Mintzer M">M.A. Mintzer</name>
</author>
<author><name sortKey="Librizzi, D" uniqKey="Librizzi D">D. Librizzi</name>
</author>
<author><name sortKey="Samsonova, O" uniqKey="Samsonova O">O. Samsonova</name>
</author>
<author><name sortKey="Dicke, T" uniqKey="Dicke T">T. Dicke</name>
</author>
<author><name sortKey="Sproat, B" uniqKey="Sproat B">B. Sproat</name>
</author>
<author><name sortKey="Garn, H" uniqKey="Garn H">H. Garn</name>
</author>
<author><name sortKey="Barth, P J" uniqKey="Barth P">P.J. Barth</name>
</author>
<author><name sortKey="Simanek, E E" uniqKey="Simanek E">E.E. Simanek</name>
</author>
<author><name sortKey="Kissel, T" uniqKey="Kissel T">T. Kissel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y. Xu</name>
</author>
<author><name sortKey="Szoka, F C" uniqKey="Szoka F">F.C. Szoka</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shete, H K" uniqKey="Shete H">H.K. Shete</name>
</author>
<author><name sortKey="Prabhu, R H" uniqKey="Prabhu R">R.H. Prabhu</name>
</author>
<author><name sortKey="Patravale, V B" uniqKey="Patravale V">V.B. Patravale</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shete, H K" uniqKey="Shete H">H.K. Shete</name>
</author>
<author><name sortKey="Prabhu, R H" uniqKey="Prabhu R">R.H. Prabhu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Urban Klein, B" uniqKey="Urban Klein B">B. Urban-Klein</name>
</author>
<author><name sortKey="Werth, S" uniqKey="Werth S">S. Werth</name>
</author>
<author><name sortKey="Abuharbeid, S" uniqKey="Abuharbeid S">S. Abuharbeid</name>
</author>
<author><name sortKey="Czubayko, F" uniqKey="Czubayko F">F. Czubayko</name>
</author>
<author><name sortKey="Aigner, A" uniqKey="Aigner A">A. Aigner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Merkel, O M" uniqKey="Merkel O">O.M. Merkel</name>
</author>
<author><name sortKey="Kissel, T" uniqKey="Kissel T">T. Kissel</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nanomaterials (Basel)</journal-id>
<journal-id journal-id-type="iso-abbrev">Nanomaterials (Basel)</journal-id>
<journal-id journal-id-type="publisher-id">nanomaterials</journal-id>
<journal-title-group><journal-title>Nanomaterials</journal-title>
</journal-title-group>
<issn pub-type="epub">2079-4991</issn>
<publisher><publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31288448</article-id>
<article-id pub-id-type="pmc">6669510</article-id>
<article-id pub-id-type="doi">10.3390/nano9070986</article-id>
<article-id pub-id-type="publisher-id">nanomaterials-09-00986</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>The Impact of Nylon-3 Copolymer Composition on the Efficiency of siRNA Delivery to Glioblastoma Cells</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hartl</surname>
<given-names>Natascha</given-names>
</name>
<xref ref-type="aff" rid="af1-nanomaterials-09-00986">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Adams</surname>
<given-names>Friederike</given-names>
</name>
<xref ref-type="aff" rid="af1-nanomaterials-09-00986">1</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-7370-1348</contrib-id>
<name><surname>Costabile</surname>
<given-names>Gabriella</given-names>
</name>
<xref ref-type="aff" rid="af1-nanomaterials-09-00986">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Isert</surname>
<given-names>Lorenz</given-names>
</name>
<xref ref-type="aff" rid="af1-nanomaterials-09-00986">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Döblinger</surname>
<given-names>Markus</given-names>
</name>
<xref ref-type="aff" rid="af2-nanomaterials-09-00986">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Xiao</surname>
<given-names>Ximian</given-names>
</name>
<xref ref-type="aff" rid="af3-nanomaterials-09-00986">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Runhui</given-names>
</name>
<xref ref-type="aff" rid="af3-nanomaterials-09-00986">3</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-4151-3916</contrib-id>
<name><surname>Merkel</surname>
<given-names>Olivia M.</given-names>
</name>
<xref ref-type="aff" rid="af1-nanomaterials-09-00986">1</xref>
<xref rid="c1-nanomaterials-09-00986" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="af1-nanomaterials-09-00986"><label>1</label>
Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Butenandtstr. 5-13, 81377 Munich, Germany</aff>
<aff id="af2-nanomaterials-09-00986"><label>2</label>
Functional Nanosystems, Department Chemistry and Biochemistry, Ludwig-Maximilians-University, Butenandtstr. 11, 81377 Munich, Germany</aff>
<aff id="af3-nanomaterials-09-00986"><label>3</label>
State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China</aff>
<author-notes><corresp id="c1-nanomaterials-09-00986"><label>*</label>
Correspondence: <email>Olivia.merkel@lmu.de</email>
; Tel.: +49-89-2180-77025</corresp>
</author-notes>
<pub-date pub-type="epub"><day>08</day>
<month>7</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><month>7</month>
<year>2019</year>
</pub-date>
<volume>9</volume>
<issue>7</issue>
<elocation-id>986</elocation-id>
<history><date date-type="received"><day>11</day>
<month>6</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>01</day>
<month>7</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 by the authors.</copyright-statement>
<copyright-year>2019</copyright-year>
<license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
).</license-p>
</license>
</permissions>
<abstract><p>Glioblastoma multiforme is a devastating disease that has attracted enormous attention due to poor prognosis and high recurrence. Small interfering RNA (siRNA) in principle offers a promising therapeutic approach by the downregulation of disease-related genes via RNA interference. For efficient siRNA delivery to target sites, cationic polymers are often used in preclinical studies for the protection of siRNA and complex formation based on electrostatic interactions. In an effort to develop biocompatible and efficient nanocarriers with a translational outlook for optimal gene silencing at reduced toxicity, we synthesized two sets of nylon-3 copolymers with variable cationic content (DM or NM monomer) and hydrophobic subunits (CP monomer) and evaluated their suitability for in vitro siRNA delivery into glioblastoma cells. DM<sub>0.4</sub>
/CP<sub>0.6</sub>
and NM<sub>0.4</sub>
/CP<sub>0.6</sub>
polymers with similar subunit ratios were synthesized to compare the effect of different cationic subunits. Additionally, we utilized NM<sub>0.2</sub>
/CP<sub>0.8</sub>
polymers to evaluate the impact of the different hydrophobic content in the polymer chain. The siRNA condensation ability and polymer–siRNA complex stability was evaluated by unmodified and modified SYBR gold assays, respectively. Further physicochemical characteristics, e.g., particle size and surface charge, were evaluated by dynamic light scattering and laser Doppler anemometry, whereas a relatively new method for polyplex size distribution analysis—tunable resistive pulse sensing—was additionally developed and compared to DLS measurements. Transfection efficiencies, the route of cell internalization, and protein knockdown abilities in glioblastoma cells were investigated by flow cytometry. Furthermore, cellular tolerability was evaluated by MTT and LDH assays. All the polymers efficiently condensed siRNA at N/P ratios of three, whereas polymers with NM cationic subunits demonstrated smaller particle size and lower polyplex stability. Furthermore, NM<sub>0.2</sub>
/CP<sub>0.8</sub>
polyplexes with the highest hydrophobic content displayed significantly higher cellular internalization in comparison to more cationic formulations and successful knockdown capabilities. Detailed investigations of the cellular uptake route demonstrated that these polyplexes mainly follow clathrin-mediated endocytotic uptake mechanisms, implying high interaction capacity with cellular membranes. Taken together with conducive toxicity profiles, highly hydrophobic nylon-3 polymers provide an appropriate siRNA delivery agent for the potential treatment of glioblastoma.</p>
</abstract>
<kwd-group><kwd>nylon-3 polymers</kwd>
<kwd>siRNA delivery</kwd>
<kwd>polyplexes</kwd>
<kwd>hydrophobically modified cationic polymers</kwd>
<kwd>glioblastoma</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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