Design of a Multicomponent Peptide-Woven Nanocomplex for Delivery of siRNA
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{"title"=>"Design of a multicomponent peptide-woven nanocomplex for delivery of siRNA", "type"=>"journal", "authors"=>[{"first_name"=>"Eunsung", "last_name"=>"Jun", "scopus_author_id"=>"55342270400"}, {"first_name"=>"Soyoun", "last_name"=>"Kim", "scopus_author_id"=>"56062024900"}, {"first_name"=>"Jong Ho", "last_name"=>"Kim", "scopus_author_id"=>"54682078400"}, {"first_name"=>"Kiweon", "last_name"=>"Cha", "scopus_author_id"=>"55342213900"}, {"first_name"=>"In Seop", "last_name"=>"So", "scopus_author_id"=>"7004320789"}, {"first_name"=>"Hye Nam", "last_name"=>"Son", "scopus_author_id"=>"35300886700"}, {"first_name"=>"Byung Heon", "last_name"=>"Lee", "scopus_author_id"=>"16304374900"}, {"first_name"=>"Kwangmeyung", "last_name"=>"Kim", "scopus_author_id"=>"35229973300"}, {"first_name"=>"Ick Chan", "last_name"=>"Kwon", "scopus_author_id"=>"7101727933"}, {"first_name"=>"Sang Yoon", "last_name"=>"Kim", "scopus_author_id"=>"35183279400"}, {"first_name"=>"In San", "last_name"=>"Kim", "scopus_author_id"=>"34770432800"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"25705892", "sgr"=>"84923315800", "doi"=>"10.1371/journal.pone.0118310", "scopus"=>"2-s2.0-84923315800", "pui"=>"602475513", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203"}, "id"=>"04824cc6-3c87-39d1-979a-9063ddb76552", "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.", "link"=>"http://www.mendeley.com/research/design-multicomponent-peptidewoven-nanocomplex-delivery-sirna", "reader_count"=>15, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>6, "Chemistry"=>3, "Chemical Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Chemistry"=>{"Chemistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Japan"=>1, "Germany"=>2}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1920919"], "description"=>"<p>(A) The relative amount of GAPDH knockdown was determined by Western blot. The intensities of immunoblot was normalized with those of beta actin control and results are presented as mean ± standard deviation (n = 5, (α) ANOVA test, P<0.05: (<sub><b>**</b></sub>) t-test, P<0.01). (B) To evaluate <i>in vivo</i> gene silencing efficacy, The HT29-luc bearing mice were treated with I4R-9r/siControl, I4R-9r/siLuciferase and I4R-9r(A1*)/sHGP-9r/siLuciferase PwSNs via intra-tumoral injection. Bio-luminescence signals of subcutaneous tumor were monitored using the IVIS Spectrum imaging system in day 0 and 4. (C) The bioluminescence intensities at tumor site were obtained and the relative intensities were calculated based on the bioluminescence intensities of each group in day 0 as 1. Error bar represents SD from three independent results.</p>", "links"=>[], "tags"=>["endosomolytic peptides", "multicomponent nanocomplex", "surface plasmon resonance analyses", "siRNA nanocomplex delivery pathway", "siRNA carriers", "9 r peptides", "4r", "siRNA delivery", "peptide models", "optimized PwSN"], "article_id"=>1315533, "categories"=>["Biological Sciences"], "users"=>["Eunsung Jun", "Soyoun Kim", "Jong-Ho Kim", "Kiweon Cha", "In-Seop So", "Hye-Nam Son", "Byung-Heon Lee", "Kwangmeyung Kim", "Ick Chan Kwon", "Sang Yoon Kim", "In-San Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118310.g004", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_I4R_9r_variant_PwSNs_mediated_gene_silencing_in_vitro_and_in_vivo_/1315533", "title"=>"I4R-9r variant PwSNs mediated gene silencing <i>in vitro</i> and <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 03:30:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1920915"], "description"=>"<p>(A) Schematic representation of the Peptide-Woven SiRNA Nanocomplex (PwSN), with siRNA noncovalently bound to I4R-9r tandem peptides composed of a tumor targeting peptide (I4R, green) and Cell penetrating peptide (9R, blue) separated by a 2-glycine spacer. (B) siRNA encapsulation by I4R-9r tandem peptides was monitored by gel retardation assay with molar ratios of 1:5 to 1:50 (siRNA-to-peptide). (C) Representative confocal microscopy images of HeLa cells treated with siRNA-FITC carried I4R-9r PwSN <i>vs</i>. free siRNA-FITC. (D) Representative histograms from flow cytometry for cellular uptake of I4R-9r PwSN (blue), 9r PwSN (grey), and free siRNA (black). (E) Representative histograms from flow cytometry for cellular uptake of I4R-9r PwSN (blue) vs. free siRNA (black) in the presence of indicated concentrations of anti-IL4R antibody or an IgG control. (F) HeLa cells were transfected with nanocomplexes carrying siRNA against GAPDH. The GAPDH protein expression is monitored by Western blot and presented with mean of relative immunoblot intensities. Lipofectamine was used as a positive control. The error bars represent SD from cumulative data of six independent experiments.</p>", "links"=>[], "tags"=>["endosomolytic peptides", "multicomponent nanocomplex", "surface plasmon resonance analyses", "siRNA nanocomplex delivery pathway", "siRNA carriers", "9 r peptides", "4r", "siRNA delivery", "peptide models", "optimized PwSN"], "article_id"=>1315529, "categories"=>["Biological Sciences"], "users"=>["Eunsung Jun", "Soyoun Kim", "Jong-Ho Kim", "Kiweon Cha", "In-Seop So", "Hye-Nam Son", "Byung-Heon Lee", "Kwangmeyung Kim", "Ick Chan Kwon", "Sang Yoon Kim", "In-San Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118310.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Design_biochemical_characterization_and_gene_silencing_activity_of_I4R_9r_PwSN_/1315529", "title"=>"Design, biochemical characterization, and gene silencing activity of I4R-9r PwSN.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 03:30:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1920923"], "description"=>"<p><sup><i>a</i></sup> sHGP-9r (RGWEVLKYWWNLLQYggRRRRRRRRR) is blended with I4R-9r/sHGP-9r PwSN with 1:19 molar ratios (sHGP-9r: I4R-9r). gg; Gly-Gly linker. Substituted alanine was highlighted by red.</p><p><sup><i>b</i></sup> Mean hydrodynamic size based on dynamic light scattering measurements. Errors indicate SD from at least three separate measurements.</p><p><sup><i>c</i></sup> Zeta-potential of nanocomplexes. Errors indicate SD from at least three independent measurements.</p><p>Structural Properties of I4R-9r/sHGP-9r PwSN variants.</p>", "links"=>[], "tags"=>["endosomolytic peptides", "multicomponent nanocomplex", "surface plasmon resonance analyses", "siRNA nanocomplex delivery pathway", "siRNA carriers", "9 r peptides", "4r", "siRNA delivery", "peptide models", "optimized PwSN"], "article_id"=>1315537, "categories"=>["Biological Sciences"], "users"=>["Eunsung Jun", "Soyoun Kim", "Jong-Ho Kim", "Kiweon Cha", "In-Seop So", "Hye-Nam Son", "Byung-Heon Lee", "Kwangmeyung Kim", "Ick Chan Kwon", "Sang Yoon Kim", "In-San Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118310.t001", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structural_Properties_of_I4R_9r_sHGP_9r_PwSN_variants_/1315537", "title"=>"Structural Properties of I4R-9r/sHGP-9r PwSN variants.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-02-23 03:30:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1920922"], "description"=>"<p>Flowchart of developing multicomponent PwSN by stepwise approach to overcome biological barriers of siRNA delivery.</p>", "links"=>[], "tags"=>["endosomolytic peptides", "multicomponent nanocomplex", "surface plasmon resonance analyses", "siRNA nanocomplex delivery pathway", "siRNA carriers", "9 r peptides", "4r", "siRNA delivery", "peptide models", "optimized PwSN"], "article_id"=>1315536, "categories"=>["Biological Sciences"], "users"=>["Eunsung Jun", "Soyoun Kim", "Jong-Ho Kim", "Kiweon Cha", "In-Seop So", "Hye-Nam Son", "Byung-Heon Lee", "Kwangmeyung Kim", "Ick Chan Kwon", "Sang Yoon Kim", "In-San Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118310.g006", "stats"=>{"downloads"=>4, "page_views"=>73, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Flowchart_of_developing_multicomponent_PwSN_by_stepwise_approach_to_overcome_biological_barriers_of_siRNA_delivery_/1315536", "title"=>"Flowchart of developing multicomponent PwSN by stepwise approach to overcome biological barriers of siRNA delivery.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 03:30:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1920920"], "description"=>"<p>(A) The released siRNA from nanocomplexes were examined upon addition of excess amount of Heparan sulfate (w:w of siRNA to Heparin sulfate as 1:5–1:40)using gel retardation assay. (B) The kinetics of association of siRNA with I4R-9r variant/sHGP-9r using SPR analysis. Increasing concentrations of I4R-9r variant/sHGP-9r peptides were injected to associate with 5`-biotinylated siRNA on the streptavidin chip. (C) The kinetics of disassociation of siRNA with I4R-9r variant/sHGP-9r using SPR analysis. After association of 5`-biotinylated siRNA with I4R-9r variant/sHGP-9r (2.5 μM) up to saturation different concentrations of heparan sulfate were injected to quantitate siRNA dissociation. The dissociation kinetics was analyzed using the Graph Prism 5.0. (D) The structures of I4R-9r variant were analyzed and compared by 3D modeling method (PEPFOLD); I4R peptide (green), Arginine of 9r (blue), Alanine (red).</p>", "links"=>[], "tags"=>["endosomolytic peptides", "multicomponent nanocomplex", "surface plasmon resonance analyses", "siRNA nanocomplex delivery pathway", "siRNA carriers", "9 r peptides", "4r", "siRNA delivery", "peptide models", "optimized PwSN"], "article_id"=>1315534, "categories"=>["Biological Sciences"], "users"=>["Eunsung Jun", "Soyoun Kim", "Jong-Ho Kim", "Kiweon Cha", "In-Seop So", "Hye-Nam Son", "Byung-Heon Lee", "Kwangmeyung Kim", "Ick Chan Kwon", "Sang Yoon Kim", "In-San Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118310.g005", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dynamic_interactions_and_structures_of_I4R_9r_variant_siRNA_nanocomplexes_/1315534", "title"=>"Dynamic interactions and structures of I4R-9r variant/siRNA nanocomplexes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 03:30:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1920917"], "description"=>"<p>(A) siRNA encapsulations by I4R-9r variants were monitored by gel retardation assay with molar ratios of 1:5 to 1:30 (siRNA: carrier) in the presence and absence of sHGP-9r. (B) Representative TEM of an I4R-9r tandem peptide variants/siRNA nanocomplex formed in water in the presence and absence of sHGP-9r; scale bar = 50 nm. (C) Stability of I4R-9r variant/sHGP-9r/siRNA nanocomplex was examined in the presence of RNase A. Undegraded siRNA of the nanocomplex was visualized on 2% agarose gel containing EtBr. The stability of free siRNA was measured as control.</p>", "links"=>[], "tags"=>["endosomolytic peptides", "multicomponent nanocomplex", "surface plasmon resonance analyses", "siRNA nanocomplex delivery pathway", "siRNA carriers", "9 r peptides", "4r", "siRNA delivery", "peptide models", "optimized PwSN"], "article_id"=>1315531, "categories"=>["Biological Sciences"], "users"=>["Eunsung Jun", "Soyoun Kim", "Jong-Ho Kim", "Kiweon Cha", "In-Seop So", "Hye-Nam Son", "Byung-Heon Lee", "Kwangmeyung Kim", "Ick Chan Kwon", "Sang Yoon Kim", "In-San Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118310.g003", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Physicochemical_characterization_of_I4R_9r_variants_PwSNs_/1315531", "title"=>"Physicochemical characterization of I4R-9r variants PwSNs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 03:30:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1920916"], "description"=>"<p>(A, Top) Confocal microscopy images of HeLa cells pretreated with the early endosome marker-RFP, and subsequently incubated with I4R-9r PwSN carrying FITC labeled siRNA. Images were pseudocolored for visualization: blue = DAPI; red = early endosome marker-RFP; green = FITC-siRNA. (A, Bottom) Confocal microscopy images of HeLa cells after treatment with FITC-siRNA encapsulated in I4R-9r PwSNs, which compose of sHGP-9r at molar ratio of 1:19 (sHGP-9r: I4R-9r). (B) The gene silencing efficacies against GAPDH protein with or without the sHGP-9r peptides was assessed by Western blot. Results are presented as mean of relative immunoblot intensities ± standard deviation (n = 6).</p>", "links"=>[], "tags"=>["endosomolytic peptides", "multicomponent nanocomplex", "surface plasmon resonance analyses", "siRNA nanocomplex delivery pathway", "siRNA carriers", "9 r peptides", "4r", "siRNA delivery", "peptide models", "optimized PwSN"], "article_id"=>1315530, "categories"=>["Biological Sciences"], "users"=>["Eunsung Jun", "Soyoun Kim", "Jong-Ho Kim", "Kiweon Cha", "In-Seop So", "Hye-Nam Son", "Byung-Heon Lee", "Kwangmeyung Kim", "Ick Chan Kwon", "Sang Yoon Kim", "In-San Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118310.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Addition_of_sHGP_9r_to_facilitate_endosome_escape_of_nanocomplexes_/1315530", "title"=>"Addition of sHGP-9r to facilitate endosome escape of nanocomplexes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-02-23 03:30:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1920924"], "description"=>"<div><p>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 <i>in vitro</i> and <i>in vivo</i>. 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.</p></div>", "links"=>[], "tags"=>["endosomolytic peptides", "multicomponent nanocomplex", "surface plasmon resonance analyses", "siRNA nanocomplex delivery pathway", "siRNA carriers", "9 r peptides", "4r", "siRNA delivery", "peptide models", "optimized PwSN"], "article_id"=>1315538, "categories"=>["Biological Sciences"], "users"=>["Eunsung Jun", "Soyoun Kim", "Jong-Ho Kim", "Kiweon Cha", "In-Seop So", "Hye-Nam Son", "Byung-Heon Lee", "Kwangmeyung Kim", "Ick Chan Kwon", "Sang Yoon Kim", "In-San Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118310", "stats"=>{"downloads"=>18, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Design_of_a_Multicomponent_Peptide_Woven_Nanocomplex_for_Delivery_of_siRNA_/1315538", "title"=>"Design of a Multicomponent Peptide-Woven Nanocomplex for Delivery of siRNA", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-02-23 03:30:14"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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