Peptide and nucleic acid-directed self-assembly of cationic nanovehicles through giant unilamellar vesicle modification: Targetable nanocomplexes for in vivo nucleic acid delivery
[Display omitted] One of the greatest challenges for the development of genetic therapies is the efficient targeted delivery of therapeutic nucleic acids. Towards this goal, we have introduced a new engineering initiative in self-assembly of biologically safe and stable nanovesicle complexes (∼90 to...
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| Veröffentlicht in: | Acta biomaterialia 2017-03, Vol.51, p.351-362 |
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| creator | Tagalakis, A.D. Maeshima, R. Yu-Wai-Man, C. Meng, J. Syed, F. Wu, L.-P. Aldossary, A.M. McCarthy, D. Moghimi, S.M. Hart, S.L. |
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One of the greatest challenges for the development of genetic therapies is the efficient targeted delivery of therapeutic nucleic acids. Towards this goal, we have introduced a new engineering initiative in self-assembly of biologically safe and stable nanovesicle complexes (∼90 to 140nm) derived from giant unilamellar vesicle (GUV) precursors and comprising plasmid DNA or siRNA and targeting peptide ligands. The biological performance of the engineered nanovesicle complexes were studied both in vitro and in vivo and compared with cationic liposome-based lipopolyplexes. Compared with cationic lipopolyplexes, nanovesicle complexes did not show advantages in transfection and cell uptake. However, nanovesicle complexes neither displayed significant cytotoxicity nor activated the complement system, which are advantageous for intravenous injection and tumour therapy. On intravenous administration into a neuroblastoma xenograft mouse model, nanovesicle complexes were found to distribute throughout the tumour interstitium, thus providing an alternative safer approach for future development of tumour-specific therapeutic nucleic acid interventions. On oropharyngeal instillation, nanovesicle complexes displayed better transfection efficiency than cationic lipopolyplexes. The technological advantages of nanovesicle complexes, originating from GUVs, over traditional cationic liposome-based lipopolyplexes are discussed.
The efficient targeted delivery of nucleic acids in vivo provides some of the greatest challenges to the development of genetic therapies. Giant unilamellar lipid vesicles (GUVs) have been used mainly as cell and tissue mimics and are instrumental in studying lipid bilayers and interactions. Here, the GUVs have been modified into smaller nanovesicles. We have then developed novel nanovesicle complexes comprising self-assembling mixtures of the nanovesicles, plasmid DNA or siRNA, and targeting peptide ligands. Their biophysical properties were studied and their transfection efficiency was investigated. They transfected cells efficiently without any associated cytotoxicity and with targeting specificity, and in vivo they resulted in very high and tumour-specific uptake and in addition, efficiently transfected the lung. The peptide-targeted nanovesicle complexes allow for the specific targeted enhancement of nucleic acid delivery with improved biosafety over liposomal formulations and represent a promising tool to improve our arsenal of |
| doi_str_mv | 10.1016/j.actbio.2017.01.048 |
| format | Article |
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One of the greatest challenges for the development of genetic therapies is the efficient targeted delivery of therapeutic nucleic acids. Towards this goal, we have introduced a new engineering initiative in self-assembly of biologically safe and stable nanovesicle complexes (∼90 to 140nm) derived from giant unilamellar vesicle (GUV) precursors and comprising plasmid DNA or siRNA and targeting peptide ligands. The biological performance of the engineered nanovesicle complexes were studied both in vitro and in vivo and compared with cationic liposome-based lipopolyplexes. Compared with cationic lipopolyplexes, nanovesicle complexes did not show advantages in transfection and cell uptake. However, nanovesicle complexes neither displayed significant cytotoxicity nor activated the complement system, which are advantageous for intravenous injection and tumour therapy. On intravenous administration into a neuroblastoma xenograft mouse model, nanovesicle complexes were found to distribute throughout the tumour interstitium, thus providing an alternative safer approach for future development of tumour-specific therapeutic nucleic acid interventions. On oropharyngeal instillation, nanovesicle complexes displayed better transfection efficiency than cationic lipopolyplexes. The technological advantages of nanovesicle complexes, originating from GUVs, over traditional cationic liposome-based lipopolyplexes are discussed.
The efficient targeted delivery of nucleic acids in vivo provides some of the greatest challenges to the development of genetic therapies. Giant unilamellar lipid vesicles (GUVs) have been used mainly as cell and tissue mimics and are instrumental in studying lipid bilayers and interactions. Here, the GUVs have been modified into smaller nanovesicles. We have then developed novel nanovesicle complexes comprising self-assembling mixtures of the nanovesicles, plasmid DNA or siRNA, and targeting peptide ligands. Their biophysical properties were studied and their transfection efficiency was investigated. They transfected cells efficiently without any associated cytotoxicity and with targeting specificity, and in vivo they resulted in very high and tumour-specific uptake and in addition, efficiently transfected the lung. The peptide-targeted nanovesicle complexes allow for the specific targeted enhancement of nucleic acid delivery with improved biosafety over liposomal formulations and represent a promising tool to improve our arsenal of safe, non-viral vectors to deliver therapeutic cargos in a variety of disorders.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2017.01.048</identifier><identifier>PMID: 28110069</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Administration, Intravenous ; Animals ; Biocompatibility ; Biophysical Phenomena ; Blotting, Western ; Cations ; Cell Line, Tumor ; Cell Survival ; Complement Activation ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; Endocytosis ; Female ; Flow Cytometry ; Gene Transfer Techniques ; GUV ; Humans ; Intravenous administration ; Lipopolyplexes ; Liposomes ; Lung - metabolism ; Mice, Inbred C57BL ; Nanoparticles - chemistry ; Neuroblastoma ; Non-viral vectors ; Nucleic acids ; Nucleic Acids - chemistry ; Peptide ; Peptides ; Peptides - chemistry ; Plasmids ; RNA, Small Interfering - metabolism ; Self-assembly ; siRNA ; Toxicity ; Transfection ; Transgenes ; Tumors ; Unilamellar Liposomes - chemistry ; Vesicles ; Xenografts</subject><ispartof>Acta biomaterialia, 2017-03, Vol.51, p.351-362</ispartof><rights>2017 Acta Materialia Inc.</rights><rights>Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Mar 15, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-ddbb374c09c96e9e725287b5bb41a4867dab61d2643df6e80a3026ad6ae008553</citedby><cites>FETCH-LOGICAL-c473t-ddbb374c09c96e9e725287b5bb41a4867dab61d2643df6e80a3026ad6ae008553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2017.01.048$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28110069$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tagalakis, A.D.</creatorcontrib><creatorcontrib>Maeshima, R.</creatorcontrib><creatorcontrib>Yu-Wai-Man, C.</creatorcontrib><creatorcontrib>Meng, J.</creatorcontrib><creatorcontrib>Syed, F.</creatorcontrib><creatorcontrib>Wu, L.-P.</creatorcontrib><creatorcontrib>Aldossary, A.M.</creatorcontrib><creatorcontrib>McCarthy, D.</creatorcontrib><creatorcontrib>Moghimi, S.M.</creatorcontrib><creatorcontrib>Hart, S.L.</creatorcontrib><title>Peptide and nucleic acid-directed self-assembly of cationic nanovehicles through giant unilamellar vesicle modification: Targetable nanocomplexes for in vivo nucleic acid delivery</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
One of the greatest challenges for the development of genetic therapies is the efficient targeted delivery of therapeutic nucleic acids. Towards this goal, we have introduced a new engineering initiative in self-assembly of biologically safe and stable nanovesicle complexes (∼90 to 140nm) derived from giant unilamellar vesicle (GUV) precursors and comprising plasmid DNA or siRNA and targeting peptide ligands. The biological performance of the engineered nanovesicle complexes were studied both in vitro and in vivo and compared with cationic liposome-based lipopolyplexes. Compared with cationic lipopolyplexes, nanovesicle complexes did not show advantages in transfection and cell uptake. However, nanovesicle complexes neither displayed significant cytotoxicity nor activated the complement system, which are advantageous for intravenous injection and tumour therapy. On intravenous administration into a neuroblastoma xenograft mouse model, nanovesicle complexes were found to distribute throughout the tumour interstitium, thus providing an alternative safer approach for future development of tumour-specific therapeutic nucleic acid interventions. On oropharyngeal instillation, nanovesicle complexes displayed better transfection efficiency than cationic lipopolyplexes. The technological advantages of nanovesicle complexes, originating from GUVs, over traditional cationic liposome-based lipopolyplexes are discussed.
The efficient targeted delivery of nucleic acids in vivo provides some of the greatest challenges to the development of genetic therapies. Giant unilamellar lipid vesicles (GUVs) have been used mainly as cell and tissue mimics and are instrumental in studying lipid bilayers and interactions. Here, the GUVs have been modified into smaller nanovesicles. We have then developed novel nanovesicle complexes comprising self-assembling mixtures of the nanovesicles, plasmid DNA or siRNA, and targeting peptide ligands. Their biophysical properties were studied and their transfection efficiency was investigated. They transfected cells efficiently without any associated cytotoxicity and with targeting specificity, and in vivo they resulted in very high and tumour-specific uptake and in addition, efficiently transfected the lung. The peptide-targeted nanovesicle complexes allow for the specific targeted enhancement of nucleic acid delivery with improved biosafety over liposomal formulations and represent a promising tool to improve our arsenal of safe, non-viral vectors to deliver therapeutic cargos in a variety of disorders.</description><subject>Administration, Intravenous</subject><subject>Animals</subject><subject>Biocompatibility</subject><subject>Biophysical Phenomena</subject><subject>Blotting, Western</subject><subject>Cations</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival</subject><subject>Complement Activation</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Endocytosis</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Gene Transfer Techniques</subject><subject>GUV</subject><subject>Humans</subject><subject>Intravenous administration</subject><subject>Lipopolyplexes</subject><subject>Liposomes</subject><subject>Lung - metabolism</subject><subject>Mice, Inbred C57BL</subject><subject>Nanoparticles - chemistry</subject><subject>Neuroblastoma</subject><subject>Non-viral vectors</subject><subject>Nucleic acids</subject><subject>Nucleic Acids - chemistry</subject><subject>Peptide</subject><subject>Peptides</subject><subject>Peptides - chemistry</subject><subject>Plasmids</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Self-assembly</subject><subject>siRNA</subject><subject>Toxicity</subject><subject>Transfection</subject><subject>Transgenes</subject><subject>Tumors</subject><subject>Unilamellar Liposomes - chemistry</subject><subject>Vesicles</subject><subject>Xenografts</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1qFTEYhoMotp56ByIB1zMm85NkXAhSWlso6KJdh_x8c04OM8kxmRk81-UNmmGq4MZNEsjzvl_Cg9A7SkpKKPt4LJWZtAtlRSgvCS1JI16gSyq4KHjLxMt85k1VcMLoBXqT0pGQWtBKvEYXlaCUENZdol_f4TQ5C1h5i_1sBnAGK-NsYV0EM4HFCYa-UCnBqIczDj02anLBZ84rHxY4uJxKeDrEMO8PeO-Un_Ds3aBGGAYV8QJpRfAYrOvdlv6EH1Xcw6R0vlh7TBhPA_zMRX2I2Hm8uCX88yJsYXALxPMVetWrIcHb532Hnm5vHq_viodvX--vvzwUpuH1VFirdc0bQzrTMeiAV20luG61bqhqBONWaUZtxZra9gwEUTWpmLJMASGibesd-rD1nmL4MUOa5DHM0eeRknasrmuyLjvUbJSJIaUIvTxFN6p4lpTI1ZQ8ys2UXE1JQmU2lWPvn8tnPYL9G_qjJgOfNwDyFxcHUSbjwBvYxEgb3P8n_AZvDasf</recordid><startdate>20170315</startdate><enddate>20170315</enddate><creator>Tagalakis, A.D.</creator><creator>Maeshima, R.</creator><creator>Yu-Wai-Man, C.</creator><creator>Meng, J.</creator><creator>Syed, F.</creator><creator>Wu, L.-P.</creator><creator>Aldossary, A.M.</creator><creator>McCarthy, D.</creator><creator>Moghimi, S.M.</creator><creator>Hart, S.L.</creator><general>Elsevier Ltd</general><general>Elsevier BV</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope></search><sort><creationdate>20170315</creationdate><title>Peptide and nucleic acid-directed self-assembly of cationic nanovehicles through giant unilamellar vesicle modification: Targetable nanocomplexes for in vivo nucleic acid delivery</title><author>Tagalakis, A.D. ; Maeshima, R. ; Yu-Wai-Man, C. ; Meng, J. ; Syed, F. ; Wu, L.-P. ; Aldossary, A.M. ; McCarthy, D. ; Moghimi, S.M. ; Hart, S.L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-ddbb374c09c96e9e725287b5bb41a4867dab61d2643df6e80a3026ad6ae008553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Administration, Intravenous</topic><topic>Animals</topic><topic>Biocompatibility</topic><topic>Biophysical Phenomena</topic><topic>Blotting, Western</topic><topic>Cations</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival</topic><topic>Complement Activation</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Endocytosis</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Gene Transfer Techniques</topic><topic>GUV</topic><topic>Humans</topic><topic>Intravenous administration</topic><topic>Lipopolyplexes</topic><topic>Liposomes</topic><topic>Lung - metabolism</topic><topic>Mice, Inbred C57BL</topic><topic>Nanoparticles - chemistry</topic><topic>Neuroblastoma</topic><topic>Non-viral vectors</topic><topic>Nucleic acids</topic><topic>Nucleic Acids - chemistry</topic><topic>Peptide</topic><topic>Peptides</topic><topic>Peptides - chemistry</topic><topic>Plasmids</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Self-assembly</topic><topic>siRNA</topic><topic>Toxicity</topic><topic>Transfection</topic><topic>Transgenes</topic><topic>Tumors</topic><topic>Unilamellar Liposomes - chemistry</topic><topic>Vesicles</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tagalakis, A.D.</creatorcontrib><creatorcontrib>Maeshima, R.</creatorcontrib><creatorcontrib>Yu-Wai-Man, C.</creatorcontrib><creatorcontrib>Meng, J.</creatorcontrib><creatorcontrib>Syed, F.</creatorcontrib><creatorcontrib>Wu, L.-P.</creatorcontrib><creatorcontrib>Aldossary, A.M.</creatorcontrib><creatorcontrib>McCarthy, D.</creatorcontrib><creatorcontrib>Moghimi, S.M.</creatorcontrib><creatorcontrib>Hart, S.L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tagalakis, A.D.</au><au>Maeshima, R.</au><au>Yu-Wai-Man, C.</au><au>Meng, J.</au><au>Syed, F.</au><au>Wu, L.-P.</au><au>Aldossary, A.M.</au><au>McCarthy, D.</au><au>Moghimi, S.M.</au><au>Hart, S.L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peptide and nucleic acid-directed self-assembly of cationic nanovehicles through giant unilamellar vesicle modification: Targetable nanocomplexes for in vivo nucleic acid delivery</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2017-03-15</date><risdate>2017</risdate><volume>51</volume><spage>351</spage><epage>362</epage><pages>351-362</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
One of the greatest challenges for the development of genetic therapies is the efficient targeted delivery of therapeutic nucleic acids. Towards this goal, we have introduced a new engineering initiative in self-assembly of biologically safe and stable nanovesicle complexes (∼90 to 140nm) derived from giant unilamellar vesicle (GUV) precursors and comprising plasmid DNA or siRNA and targeting peptide ligands. The biological performance of the engineered nanovesicle complexes were studied both in vitro and in vivo and compared with cationic liposome-based lipopolyplexes. Compared with cationic lipopolyplexes, nanovesicle complexes did not show advantages in transfection and cell uptake. However, nanovesicle complexes neither displayed significant cytotoxicity nor activated the complement system, which are advantageous for intravenous injection and tumour therapy. On intravenous administration into a neuroblastoma xenograft mouse model, nanovesicle complexes were found to distribute throughout the tumour interstitium, thus providing an alternative safer approach for future development of tumour-specific therapeutic nucleic acid interventions. On oropharyngeal instillation, nanovesicle complexes displayed better transfection efficiency than cationic lipopolyplexes. The technological advantages of nanovesicle complexes, originating from GUVs, over traditional cationic liposome-based lipopolyplexes are discussed.
The efficient targeted delivery of nucleic acids in vivo provides some of the greatest challenges to the development of genetic therapies. Giant unilamellar lipid vesicles (GUVs) have been used mainly as cell and tissue mimics and are instrumental in studying lipid bilayers and interactions. Here, the GUVs have been modified into smaller nanovesicles. We have then developed novel nanovesicle complexes comprising self-assembling mixtures of the nanovesicles, plasmid DNA or siRNA, and targeting peptide ligands. Their biophysical properties were studied and their transfection efficiency was investigated. They transfected cells efficiently without any associated cytotoxicity and with targeting specificity, and in vivo they resulted in very high and tumour-specific uptake and in addition, efficiently transfected the lung. The peptide-targeted nanovesicle complexes allow for the specific targeted enhancement of nucleic acid delivery with improved biosafety over liposomal formulations and represent a promising tool to improve our arsenal of safe, non-viral vectors to deliver therapeutic cargos in a variety of disorders.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28110069</pmid><doi>10.1016/j.actbio.2017.01.048</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Acta biomaterialia, 2017-03, Vol.51, p.351-362 |
| issn | 1742-7061 1878-7568 |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Administration, Intravenous Animals Biocompatibility Biophysical Phenomena Blotting, Western Cations Cell Line, Tumor Cell Survival Complement Activation Cytotoxicity Deoxyribonucleic acid DNA Endocytosis Female Flow Cytometry Gene Transfer Techniques GUV Humans Intravenous administration Lipopolyplexes Liposomes Lung - metabolism Mice, Inbred C57BL Nanoparticles - chemistry Neuroblastoma Non-viral vectors Nucleic acids Nucleic Acids - chemistry Peptide Peptides Peptides - chemistry Plasmids RNA, Small Interfering - metabolism Self-assembly siRNA Toxicity Transfection Transgenes Tumors Unilamellar Liposomes - chemistry Vesicles Xenografts |
| title | Peptide and nucleic acid-directed self-assembly of cationic nanovehicles through giant unilamellar vesicle modification: Targetable nanocomplexes for in vivo nucleic acid delivery |
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