期刊
ACS NANO
卷 6, 期 3, 页码 2198-2214出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn204116u
关键词
nanohydrogel; block copolymer; reactive ester; RAFT polymerization; self-assembled aggregates; siRNA delivery
类别
资金
- Institute of Molecular Biology (IMB), Mainz
- SAMT
- COMATT
- Fond der Chemischen Industrie
- Max Planck Graduate School
Oligonucleotides such as short, double-stranded RNA (siRNA) or plasmid DNA (pDNA) promise high potential in gene therapy. For pharmaceutical application, however, adequate drug carriers are required. Among various concepts progressing in the market or final development, nanosized hydrogel particles may serve as novel transport media especially for siRNA. In this work, a new concept of synthesizing polymeric cationic nanohydrogels was developed, which offers a promising strategy to complex and transport siRNA into cells. For this purpose, amphiphilic reactive ester block copolymers were synthesized by RAFT polymerization of pentafluorophenyl methacrylate as reactive ester monomer together with tri(ethylene glycol)methyl ether methacrylate. In polar aprotic solvents, a self-assembly of these polymers could be observed leading to the formation of nanometer-sized polymer aggregates. The resulting superstructures were used to convert the reactive precursor block copolymers with amine-containing cross-linker molecules Into covalently stabilized hydrogel particles. Detailed dynamic light mattering studies showed that the structure of the self-assembled aggregates can permanently be locked-in by this process. This method offers a new possibility to synthesize precise nanohydrogels of different size starting from various block copolymers. Moreover, via reactive ester approach, further functionalities could be attached to the nanoparticle, such as fluorescent dyes, which allowed distinct tracing of the hydrogels during complexation with siRNA or cell uptake experiments. In this respect, cellular uptake of the particles themselves as well as with its payload could be detected successfully. Looking ahead, these novel cationic nanohydrogel particles may serve as a new platform for proper siRNA delivery systems.
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