COINS Seminar #12
Cationic Nanohydrogel Particles as Safe Carriers
for Therapeutic Oligonucleotide Delivery

N. Leber, L. Nuhn, R. Zentel
Institute of Organic Chemistry, Johannes Gutenberg-University of Mainz
Date:Friday,December 4,2015
Time:16:00～17:00
Venue:Room #56,Engineering building #5,
The University of Tokyo（会場：東京大学工学部 5 号館 56 号講義室）—Abstract—
Pharmaceutically active oligonucleotides (e.g siRNA) require adequate
carriers for targeted and safe transport through the body, crossing
membrane barriers and controlled release of their payload at the site ofaction. In contrast to lipoplex or polyplex formulations, cationic nanogels
can serve as alternative oligonucleotide carriers. Usually they have preadjusted superstructures independent from their polyanionic cargo and show great stability, especially inpresence of further polyanionic competitors. To this respect, we developed a novel concept forsynthesizing polymeric cationic nanohydrogels,[1] which provides a safe and stable environment forsiRNA, avoids carrier aggregation under physiologically relevant conditions[2] and promotes sizedependent gene silencing in vitro.[3] Via RAFT polymerization well-defined block copolymers ofpentafluorophenyl methacrylate and tri(ethylene glycol) methyl ether methacrylate were synthesized that
self-assemble in polar aprotic solvents (e.g. DMSO) into nm-sized polymer micelles. The resulting
superstructures were used to generate cationic nanohydrogel particles by covalently cross-linking thereactive ester cores with spermine providing cationic moieties for stable siRNA complexation.[2]Interestingly, the synthetic process offers possibilities to synthesize nanohydrogels of various sizes, whichshow a size-dependent gene silencing potential in vitro.[3] Presently, we are working on the introductionof groups for active targetting and degradable cross-linkers for stimuli-responsive siRNA release.[4]Looking ahead, these novel cationic nanohydrogel particles can also serve as platform for advanced
therapeutic oligonucleotide delivery strategies in the field of cancer immunotherapy.[5][1]L. Nuhn, M. Hirsch, B. Krieg, K. Koynov, K. Fischer, M. Schmidt, M. Helm, M.; R. Zentel, ACS
Nano 2012, 6, 2198.
[2]
L. Nuhn, S. Gietzen, K. Mohr, K. Fischer, K. Toh, K. Miyata, Y. Matsumoto, K. Kataoka, K., M.
Schmidt, R. Zentel. Biomacromolecules 2014, 15, 1526.
[3]
L. Nuhn, S. Tomcin, K. Miyata, V. Mailänder, K. Landfester, K. Kataoka, R. Zentel,
Biomacromolecules 2014, DOI:10.1021/bm501148y.
[4]
L. Nuhn, L. Braun, I. Overhoff, A. Kelsch, D. Schaeffel, K. Koynov, R. Zentel, Macromol. Rapid
Commun. 2014, 35, 2057−2064[5]
S. Hartmann, L. Nuhn, B. Paliztsch, M. Glaffig, N. Stergiou,B. Gerlitzki, E. Schmitt, H. Kunz, R.
Zentel, Adv. Healthcare Mater. 2014, 4, 522 -527
＊Organizer: Center of Innovation (COI program) by JST
Kazunori Kataoka, Research Leader, Kawasaki Institute of Industrial Promotion, Innovation Center of Nanomedicine (iCONM)
and Professor. Graduate Schools of Engineering / Medicine, The University of Tokyo＊For Further Information Contact: COINS Research Support Office E-mail: jimukyoku-coins@kawasaki-net.ne.jp
Web: http://coins.kawasaki-net.ne.jp

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