Jun, Eunsung Kim, Soyoun Kim, Jong-Ho Cha, Kiweon So, In-Seop Son, Hye-Nam Lee, Byung-Heon Kim, Kwangmeyung Kwon, Ick Chan Kim, Sang Yoon Kim, In-San 2024-01-20T07:34:02Z 2024-01-20T07:34:02Z 2021-09-04 2015-02-23 1932-6203 https://pubs.kist.re.kr/handle/201004/125753 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. English PUBLIC LIBRARY SCIENCE DE-NOVO PEPTIDE STRUCTURE PREDICTION INTRACELLULAR DELIVERY MOLECULAR-DYNAMICS ENDOSOMAL ESCAPE INTERFERING RNA CELLULAR UPTAKE CANCER-THERAPY PEP-FOLD GENE Design of a Multicomponent Peptide-Woven Nanocomplex for Delivery of siRNA Article 10.1371/journal.pone.0118310 1 PLOS ONE, v.10, no.2 PLOS ONE 10 2 scie scopus 000350662100165 2-s2.0-84923315800 Multidisciplinary Sciences Science & Technology - Other Topics Article DE-NOVO PEPTIDE STRUCTURE PREDICTION INTRACELLULAR DELIVERY MOLECULAR-DYNAMICS ENDOSOMAL ESCAPE INTERFERING RNA CELLULAR UPTAKE CANCER-THERAPY PEP-FOLD GENE