Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model
Abstract Therapeutic strategies based on modulation of microRNA activity possess much promise in cancer therapy, but the in vivo delivery of microRNA to target sites and its penetration into tumor tissues remain great challenge. In this work, miR-34a-delivering therapeutic nanocomplexes with a tumor...
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| Veröffentlicht in: | Biomaterials 2013-03, Vol.34 (9), p.2265-2276 |
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| creator | Hu, Q.L Jiang, Q.Y Jin, X Shen, J Wang, K Li, Y.B Xu, F.J Tang, G.P Li, Z.H |
| description | Abstract Therapeutic strategies based on modulation of microRNA activity possess much promise in cancer therapy, but the in vivo delivery of microRNA to target sites and its penetration into tumor tissues remain great challenge. In this work, miR-34a-delivering therapeutic nanocomplexes with a tumor-targeting and -penetrating bifunctional CC9 peptide were proposed for efficient treatment of pancreatic cancers. In vitro study indicated that the nanoparticle-based miR-34a delivery systems could effectively facilitate cellular uptake and greatly up-regulate the mRNA level of miR-34a in PANC-1 cell lines. The up-regulation of miR-34a remarkably induced cell cycle arrest and apoptosis, suppressed the tumor cell migration and inhibited the target gene expressions such as E2F3, Bcl-2, c-myc and cyclin D1. More importantly, the in vivo systemic administration of the developed targeting miR-34a delivery systems in a pancreatic cancer model significantly inhibited tumor growth and induced cancer cell apoptosis. Such bifunctional peptide-conjugated miRNA-delivering nanocomplexes should have great potential applications in cancer therapy. |
| doi_str_mv | 10.1016/j.biomaterials.2012.12.016 |
| format | Article |
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In this work, miR-34a-delivering therapeutic nanocomplexes with a tumor-targeting and -penetrating bifunctional CC9 peptide were proposed for efficient treatment of pancreatic cancers. In vitro study indicated that the nanoparticle-based miR-34a delivery systems could effectively facilitate cellular uptake and greatly up-regulate the mRNA level of miR-34a in PANC-1 cell lines. The up-regulation of miR-34a remarkably induced cell cycle arrest and apoptosis, suppressed the tumor cell migration and inhibited the target gene expressions such as E2F3, Bcl-2, c-myc and cyclin D1. More importantly, the in vivo systemic administration of the developed targeting miR-34a delivery systems in a pancreatic cancer model significantly inhibited tumor growth and induced cancer cell apoptosis. Such bifunctional peptide-conjugated miRNA-delivering nanocomplexes should have great potential applications in cancer therapy.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2012.12.016</identifier><identifier>PMID: 23298779</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Animals ; Apoptosis ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Blotting, Western ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cyclin D1 - genetics ; Cyclin D1 - metabolism ; Dentistry ; E2F3 Transcription Factor - genetics ; E2F3 Transcription Factor - metabolism ; Gene Expression Regulation, Neoplastic ; Gene Transfer Techniques ; Humans ; Mice ; Mice, Inbred BALB C ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Nanoparticle ; Nanoparticles - chemistry ; Nanotechnology - methods ; Pancreatic cancer therapy ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Pancreatic Neoplasms - therapy ; Peptide ; Peptides - chemistry ; PET ; Proto-Oncogene Proteins c-myc - genetics ; Proto-Oncogene Proteins c-myc - metabolism ; Up-Regulation ; Xenograft Model Antitumor Assays</subject><ispartof>Biomaterials, 2013-03, Vol.34 (9), p.2265-2276</ispartof><rights>Elsevier Ltd</rights><rights>2012 Elsevier Ltd</rights><rights>Copyright © 2012 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-3cf4bb37a51ac4a0139a895c86708ec4b4c972d4e6a6f2a7a5b07118a32e1ae43</citedby><cites>FETCH-LOGICAL-c435t-3cf4bb37a51ac4a0139a895c86708ec4b4c972d4e6a6f2a7a5b07118a32e1ae43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0142961212013968$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23298779$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Q.L</creatorcontrib><creatorcontrib>Jiang, Q.Y</creatorcontrib><creatorcontrib>Jin, X</creatorcontrib><creatorcontrib>Shen, J</creatorcontrib><creatorcontrib>Wang, K</creatorcontrib><creatorcontrib>Li, Y.B</creatorcontrib><creatorcontrib>Xu, F.J</creatorcontrib><creatorcontrib>Tang, G.P</creatorcontrib><creatorcontrib>Li, Z.H</creatorcontrib><title>Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Therapeutic strategies based on modulation of microRNA activity possess much promise in cancer therapy, but the in vivo delivery of microRNA to target sites and its penetration into tumor tissues remain great challenge. In this work, miR-34a-delivering therapeutic nanocomplexes with a tumor-targeting and -penetrating bifunctional CC9 peptide were proposed for efficient treatment of pancreatic cancers. In vitro study indicated that the nanoparticle-based miR-34a delivery systems could effectively facilitate cellular uptake and greatly up-regulate the mRNA level of miR-34a in PANC-1 cell lines. The up-regulation of miR-34a remarkably induced cell cycle arrest and apoptosis, suppressed the tumor cell migration and inhibited the target gene expressions such as E2F3, Bcl-2, c-myc and cyclin D1. More importantly, the in vivo systemic administration of the developed targeting miR-34a delivery systems in a pancreatic cancer model significantly inhibited tumor growth and induced cancer cell apoptosis. Such bifunctional peptide-conjugated miRNA-delivering nanocomplexes should have great potential applications in cancer therapy.</description><subject>Advanced Basic Science</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Blotting, Western</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cyclin D1 - genetics</subject><subject>Cyclin D1 - metabolism</subject><subject>Dentistry</subject><subject>E2F3 Transcription Factor - genetics</subject><subject>E2F3 Transcription Factor - metabolism</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Transfer Techniques</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Nanoparticle</subject><subject>Nanoparticles - chemistry</subject><subject>Nanotechnology - methods</subject><subject>Pancreatic cancer therapy</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pancreatic Neoplasms - therapy</subject><subject>Peptide</subject><subject>Peptides - chemistry</subject><subject>PET</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Proto-Oncogene Proteins c-myc - metabolism</subject><subject>Up-Regulation</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkl1vFCEUhomxsdvqXzDEK29m5Wu-vDDZrFZNmmr8uCYMc6isM7ACs7X_Xsi2jfHKhATIed_3wAMIvaBkTQltXu3Wg_WzShCsmuKaEcrWeeTSI7SiXdtVdU_qx2hFqGBV31B2is5i3JG8J4I9QaeMs75r236Flq1K1jur8Wx18F-uNtUIkz3kbHeNnXL-ADr5EPGNTT_wYM3idHGoCe9hn-wIERsfMBhjtQWXcAqg0lxW3uDPm6ttRfFvcP46KJPw7HP-U3Ri8tHh2d18jr5fvPu2_VBdfnr_cbu5rLTgdaq4NmIYeKtqqrRQhPJedX2tu6YlHWgxCN23bBTQqMYwlXUDaSntFGdAFQh-jl4ec_fB_1ogJjnbqGGalAO_RElZy5ue8IZm6eujNFOIMYCR-2BnFW4lJbJglzv5N3ZZsOcAmUvZ_PyuzzLMMD5Y7zlnwdujAPJtDxaCjAWWhtGGzFeO3v5fnzf_xOjJ5sdT00-4hbjzS3DFQ2XMBvm1fIDy_pQVdk3H_wCWH7F1</recordid><startdate>20130301</startdate><enddate>20130301</enddate><creator>Hu, Q.L</creator><creator>Jiang, Q.Y</creator><creator>Jin, X</creator><creator>Shen, J</creator><creator>Wang, K</creator><creator>Li, Y.B</creator><creator>Xu, F.J</creator><creator>Tang, G.P</creator><creator>Li, Z.H</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130301</creationdate><title>Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model</title><author>Hu, Q.L ; Jiang, Q.Y ; Jin, X ; Shen, J ; Wang, K ; Li, Y.B ; Xu, F.J ; Tang, G.P ; Li, Z.H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-3cf4bb37a51ac4a0139a895c86708ec4b4c972d4e6a6f2a7a5b07118a32e1ae43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Advanced Basic Science</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Blotting, Western</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cyclin D1 - genetics</topic><topic>Cyclin D1 - metabolism</topic><topic>Dentistry</topic><topic>E2F3 Transcription Factor - genetics</topic><topic>E2F3 Transcription Factor - metabolism</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Transfer Techniques</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Nanoparticle</topic><topic>Nanoparticles - chemistry</topic><topic>Nanotechnology - methods</topic><topic>Pancreatic cancer therapy</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pancreatic Neoplasms - therapy</topic><topic>Peptide</topic><topic>Peptides - chemistry</topic><topic>PET</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Proto-Oncogene Proteins c-myc - metabolism</topic><topic>Up-Regulation</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Q.L</creatorcontrib><creatorcontrib>Jiang, Q.Y</creatorcontrib><creatorcontrib>Jin, X</creatorcontrib><creatorcontrib>Shen, J</creatorcontrib><creatorcontrib>Wang, K</creatorcontrib><creatorcontrib>Li, Y.B</creatorcontrib><creatorcontrib>Xu, F.J</creatorcontrib><creatorcontrib>Tang, G.P</creatorcontrib><creatorcontrib>Li, Z.H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Q.L</au><au>Jiang, Q.Y</au><au>Jin, X</au><au>Shen, J</au><au>Wang, K</au><au>Li, Y.B</au><au>Xu, F.J</au><au>Tang, G.P</au><au>Li, Z.H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2013-03-01</date><risdate>2013</risdate><volume>34</volume><issue>9</issue><spage>2265</spage><epage>2276</epage><pages>2265-2276</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract Therapeutic strategies based on modulation of microRNA activity possess much promise in cancer therapy, but the in vivo delivery of microRNA to target sites and its penetration into tumor tissues remain great challenge. In this work, miR-34a-delivering therapeutic nanocomplexes with a tumor-targeting and -penetrating bifunctional CC9 peptide were proposed for efficient treatment of pancreatic cancers. In vitro study indicated that the nanoparticle-based miR-34a delivery systems could effectively facilitate cellular uptake and greatly up-regulate the mRNA level of miR-34a in PANC-1 cell lines. The up-regulation of miR-34a remarkably induced cell cycle arrest and apoptosis, suppressed the tumor cell migration and inhibited the target gene expressions such as E2F3, Bcl-2, c-myc and cyclin D1. More importantly, the in vivo systemic administration of the developed targeting miR-34a delivery systems in a pancreatic cancer model significantly inhibited tumor growth and induced cancer cell apoptosis. Such bifunctional peptide-conjugated miRNA-delivering nanocomplexes should have great potential applications in cancer therapy.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>23298779</pmid><doi>10.1016/j.biomaterials.2012.12.016</doi><tpages>12</tpages></addata></record> |
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| ispartof | Biomaterials, 2013-03, Vol.34 (9), p.2265-2276 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Advanced Basic Science Animals Apoptosis bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Blotting, Western Cell Line, Tumor Cell Movement Cell Proliferation Cyclin D1 - genetics Cyclin D1 - metabolism Dentistry E2F3 Transcription Factor - genetics E2F3 Transcription Factor - metabolism Gene Expression Regulation, Neoplastic Gene Transfer Techniques Humans Mice Mice, Inbred BALB C MicroRNAs - genetics MicroRNAs - metabolism miRNA Nanoparticle Nanoparticles - chemistry Nanotechnology - methods Pancreatic cancer therapy Pancreatic Neoplasms - genetics Pancreatic Neoplasms - pathology Pancreatic Neoplasms - therapy Peptide Peptides - chemistry PET Proto-Oncogene Proteins c-myc - genetics Proto-Oncogene Proteins c-myc - metabolism Up-Regulation Xenograft Model Antitumor Assays |
| title | Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model |
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