Design of a Multicomponent Peptide-Woven Nanocomplex for Delivery of siRNA

Authors
Jun, EunsungKim, SoyounKim, Jong-HoCha, KiweonSo, In-SeopSon, Hye-NamLee, Byung-HeonKim, KwangmeyungKwon, Ick ChanKim, Sang YoonKim, In-San
Issue Date
2015-02-23
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.10, no.2
Abstract
We developed and tested a multicomponent peptide-woven siRNA nanocomplex (PwSN) comprising different peptides designed for efficient cellular targeting, endosomal escape, and release of siRNA. To enhance tumor-specific cellular uptake, we connected an interleukin-4 receptor-targeting peptide (I4R) to a nine-arginine peptide (9r), yielding I4R-9r. To facilitate endosomal escape, we blended endosomolytic peptides into the I4R-9r to form a multicomponent nanocomplex. Lastly, we modified 9r peptides by varying the number and positions of positive charges to obtain efficient release of siRNA from the nanocomplex in the cytosol. Using this step-wise approach for overcoming the biological challenges of siRNA delivery, we obtained an optimized PwSN with significant biological activity in vitro and in vivo. Interestingly, surface plasmon resonance analyses and three-dimensional peptide models demonstrated that our designed peptide adopted a unique structure that was correlated with faster complex disassembly and a better gene-silencing effect. These studies further elucidate the siRNA nanocomplex delivery pathway and demonstrate the applicability of our stepwise strategy to the design of siRNA carriers capable of overcoming multiple challenges and achieving efficient delivery.
Keywords
DE-NOVO PEPTIDE; STRUCTURE PREDICTION; INTRACELLULAR DELIVERY; MOLECULAR-DYNAMICS; ENDOSOMAL ESCAPE; INTERFERING RNA; CELLULAR UPTAKE; CANCER-THERAPY; PEP-FOLD; GENE; DE-NOVO PEPTIDE; STRUCTURE PREDICTION; INTRACELLULAR DELIVERY; MOLECULAR-DYNAMICS; ENDOSOMAL ESCAPE; INTERFERING RNA; CELLULAR UPTAKE; CANCER-THERAPY; PEP-FOLD; GENE
ISSN
1932-6203
URI
https://pubs.kist.re.kr/handle/201004/125753
DOI
10.1371/journal.pone.0118310
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KIST Article > 2015
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