Model Affitin and PEG modifications onto siRNA lipid nanocapsules: cell uptake and in vivo biodistribution improvements
Malignant melanoma is an aggressive tumor, associated with the presence of local and/or distant metastases. The development of gene therapy by the use of small interfering RNA (siRNA) represents a promising new treatment. However, the protection of this biomolecule is necessary in order for it to be...
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| creator | Resnier, Pauline Lepeltier, Elise Emina, Anthea Lucrezia Galopin, Natacha Bejaud, Jérôme David, Stephanie Ballet, Caroline Benvegnu, Thierry Pecorari, Frédéric Chourpa, Igor Benoit, Jean-Pierre Passirani, Catherine |
| description | Malignant melanoma is an aggressive tumor, associated with the presence of local and/or distant metastases. The development of gene therapy by the use of small interfering RNA (siRNA) represents a promising new treatment. However, the protection of this biomolecule is necessary in order for it to be intravenously administrated, for example
its incorporation into nanomedicines. In parallel to the passive targeting usually obtained by pegylation, various studies have aimed at developing "smart" nanomedicines to efficiently deliver the drug to tumor sites. In this work, siRNA loaded lipid nanocapsules (LNCs) were modified with DSPE-polyethylene glycol (DSPE-PEG), tetraether-PEG (TE-PEG) and/or with an Affitin model, to assay multiple targeting strategies. The uptake of fluorescently labelled LNCs, nanocarrier integrity and siRNA release into human SK-Mel28 melanoma cells were studied by flow cytometry, conventional confocal microscopy and by confocal spectral imaging in a Förster Resonance Energy Transfer (FRET) mode. Surface modified siRNA LNCs were followed after human plasma incubation and after intravenous injection, in order to compare the stealth properties. Finally, the biodistribution of the different siRNA LNCs in healthy and melanoma tumor bearing mice models was assessed by
biofluorescence imaging (BFI), to evaluate the potential tumor targeting ability. The post-insertion of DSPE-PEG induced a strong decrease of the internalization into melanoma cells compared to TE-PEG modification. Both PEG polymer decorations induced a great plasma protection of siRNA but only DSPE-PEG led to stealth properties, even at low concentration (5 mM). The Affitin grafting by thiolation of DSPE-PEG was validated on siRNA LNCs. DSPE-PEG-Affitin LNCs were not detected in this melanoma tumor model but did not show unspecific accumulation in organs. DSPE-PEG and TE-PEG LNCs induced a significant intratumoral accumulation of modified LNCs. |
| doi_str_mv | 10.1039/c9ra03668g |
| format | Article |
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its incorporation into nanomedicines. In parallel to the passive targeting usually obtained by pegylation, various studies have aimed at developing "smart" nanomedicines to efficiently deliver the drug to tumor sites. In this work, siRNA loaded lipid nanocapsules (LNCs) were modified with DSPE-polyethylene glycol (DSPE-PEG), tetraether-PEG (TE-PEG) and/or with an Affitin model, to assay multiple targeting strategies. The uptake of fluorescently labelled LNCs, nanocarrier integrity and siRNA release into human SK-Mel28 melanoma cells were studied by flow cytometry, conventional confocal microscopy and by confocal spectral imaging in a Förster Resonance Energy Transfer (FRET) mode. Surface modified siRNA LNCs were followed after human plasma incubation and after intravenous injection, in order to compare the stealth properties. Finally, the biodistribution of the different siRNA LNCs in healthy and melanoma tumor bearing mice models was assessed by
biofluorescence imaging (BFI), to evaluate the potential tumor targeting ability. The post-insertion of DSPE-PEG induced a strong decrease of the internalization into melanoma cells compared to TE-PEG modification. Both PEG polymer decorations induced a great plasma protection of siRNA but only DSPE-PEG led to stealth properties, even at low concentration (5 mM). The Affitin grafting by thiolation of DSPE-PEG was validated on siRNA LNCs. DSPE-PEG-Affitin LNCs were not detected in this melanoma tumor model but did not show unspecific accumulation in organs. DSPE-PEG and TE-PEG LNCs induced a significant intratumoral accumulation of modified LNCs.</description><identifier>ISSN: 2046-2069</identifier><identifier>EISSN: 2046-2069</identifier><identifier>DOI: 10.1039/c9ra03668g</identifier><identifier>PMID: 35529231</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Accumulation ; animal models ; Biomolecules ; Blood plasma ; Cancer ; chemical bonding ; Chemistry ; confocal microscopy ; Drug delivery systems ; drugs ; Energy transfer ; Flow cytometry ; Gene therapy ; humans ; image analysis ; intravenous injection ; Life Sciences ; Lipids ; Melanoma ; metastasis ; nanocapsules ; nanocarriers ; nanomedicine ; Organs ; Polyethylene glycol ; polymers ; Skin cancer ; small interfering RNA ; Tumors</subject><ispartof>RSC advances, 2019-08, Vol.9 (47), p.27264-27278</ispartof><rights>This journal is © The Royal Society of Chemistry.</rights><rights>Copyright Royal Society of Chemistry 2019</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>This journal is © The Royal Society of Chemistry 2019 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-e77ac912f786c88d8340d331d84650c3b764cf52740092e30c3e2a3f6b905dcc3</citedby><cites>FETCH-LOGICAL-c517t-e77ac912f786c88d8340d331d84650c3b764cf52740092e30c3e2a3f6b905dcc3</cites><orcidid>0000-0001-6024-7839 ; 0000-0002-7666-6453 ; 0000-0003-2116-0735 ; 0000-0002-7854-0643 ; 0000-0003-1613-9990</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070605/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070605/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35529231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-02337070$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Resnier, Pauline</creatorcontrib><creatorcontrib>Lepeltier, Elise</creatorcontrib><creatorcontrib>Emina, Anthea Lucrezia</creatorcontrib><creatorcontrib>Galopin, Natacha</creatorcontrib><creatorcontrib>Bejaud, Jérôme</creatorcontrib><creatorcontrib>David, Stephanie</creatorcontrib><creatorcontrib>Ballet, Caroline</creatorcontrib><creatorcontrib>Benvegnu, Thierry</creatorcontrib><creatorcontrib>Pecorari, Frédéric</creatorcontrib><creatorcontrib>Chourpa, Igor</creatorcontrib><creatorcontrib>Benoit, Jean-Pierre</creatorcontrib><creatorcontrib>Passirani, Catherine</creatorcontrib><title>Model Affitin and PEG modifications onto siRNA lipid nanocapsules: cell uptake and in vivo biodistribution improvements</title><title>RSC advances</title><addtitle>RSC Adv</addtitle><description>Malignant melanoma is an aggressive tumor, associated with the presence of local and/or distant metastases. The development of gene therapy by the use of small interfering RNA (siRNA) represents a promising new treatment. However, the protection of this biomolecule is necessary in order for it to be intravenously administrated, for example
its incorporation into nanomedicines. In parallel to the passive targeting usually obtained by pegylation, various studies have aimed at developing "smart" nanomedicines to efficiently deliver the drug to tumor sites. In this work, siRNA loaded lipid nanocapsules (LNCs) were modified with DSPE-polyethylene glycol (DSPE-PEG), tetraether-PEG (TE-PEG) and/or with an Affitin model, to assay multiple targeting strategies. The uptake of fluorescently labelled LNCs, nanocarrier integrity and siRNA release into human SK-Mel28 melanoma cells were studied by flow cytometry, conventional confocal microscopy and by confocal spectral imaging in a Förster Resonance Energy Transfer (FRET) mode. Surface modified siRNA LNCs were followed after human plasma incubation and after intravenous injection, in order to compare the stealth properties. Finally, the biodistribution of the different siRNA LNCs in healthy and melanoma tumor bearing mice models was assessed by
biofluorescence imaging (BFI), to evaluate the potential tumor targeting ability. The post-insertion of DSPE-PEG induced a strong decrease of the internalization into melanoma cells compared to TE-PEG modification. Both PEG polymer decorations induced a great plasma protection of siRNA but only DSPE-PEG led to stealth properties, even at low concentration (5 mM). The Affitin grafting by thiolation of DSPE-PEG was validated on siRNA LNCs. DSPE-PEG-Affitin LNCs were not detected in this melanoma tumor model but did not show unspecific accumulation in organs. DSPE-PEG and TE-PEG LNCs induced a significant intratumoral accumulation of modified LNCs.</description><subject>Accumulation</subject><subject>animal models</subject><subject>Biomolecules</subject><subject>Blood plasma</subject><subject>Cancer</subject><subject>chemical bonding</subject><subject>Chemistry</subject><subject>confocal microscopy</subject><subject>Drug delivery systems</subject><subject>drugs</subject><subject>Energy transfer</subject><subject>Flow cytometry</subject><subject>Gene therapy</subject><subject>humans</subject><subject>image analysis</subject><subject>intravenous injection</subject><subject>Life Sciences</subject><subject>Lipids</subject><subject>Melanoma</subject><subject>metastasis</subject><subject>nanocapsules</subject><subject>nanocarriers</subject><subject>nanomedicine</subject><subject>Organs</subject><subject>Polyethylene glycol</subject><subject>polymers</subject><subject>Skin cancer</subject><subject>small interfering RNA</subject><subject>Tumors</subject><issn>2046-2069</issn><issn>2046-2069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkltvFCEUgInR2Gbtiz_AkPhijKtcBgZ8MJls6tZkvaTRZ8IA01JnYAozY_z3st3a1L7IyyGHj--QwwHgOUZvMaLynZFJI8q5uHgEjgmq-JogLh_f2x-Bk5yvUFmcYcLxU3BEGSOSUHwMfn2O1vWw6To_-QB1sPDb6RYO0frOGz35GDKMYYow-_MvDez96C0MOkSjxzz3Lr-HxvU9nMdJ_3Q3guJZ_BJh64slT8m3894D_TCmuLjBhSk_A0863Wd3chtX4MfH0--bs_Xu6_bTptmtDcP1tHZ1rY3EpKsFN0JYQStkKcVWVJwhQ9uaV6ZjpK4QksTRknJE0463EjFrDF2BDwfvOLeDs6bUTrpXY_KDTr9V1F79exL8pbqIi5KoRhyxInhzEFw-uHbW7JQP2aVBIUJpXfgFF_zVbb0Ur2eXJzX4vG-QDi7OWRHOcSU4l9X_UYoYFliSvfXlA_QqzimUxilCBC2_XJWwAq8PlEkx5-S6u_dipPbDojbyvLkZlm2BX9xvzB36dzToHxzUucs</recordid><startdate>20190830</startdate><enddate>20190830</enddate><creator>Resnier, Pauline</creator><creator>Lepeltier, Elise</creator><creator>Emina, Anthea Lucrezia</creator><creator>Galopin, Natacha</creator><creator>Bejaud, Jérôme</creator><creator>David, Stephanie</creator><creator>Ballet, Caroline</creator><creator>Benvegnu, Thierry</creator><creator>Pecorari, Frédéric</creator><creator>Chourpa, Igor</creator><creator>Benoit, Jean-Pierre</creator><creator>Passirani, Catherine</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7S9</scope><scope>L.6</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6024-7839</orcidid><orcidid>https://orcid.org/0000-0002-7666-6453</orcidid><orcidid>https://orcid.org/0000-0003-2116-0735</orcidid><orcidid>https://orcid.org/0000-0002-7854-0643</orcidid><orcidid>https://orcid.org/0000-0003-1613-9990</orcidid></search><sort><creationdate>20190830</creationdate><title>Model Affitin and PEG modifications onto siRNA lipid nanocapsules: cell uptake and in vivo biodistribution improvements</title><author>Resnier, Pauline ; Lepeltier, Elise ; Emina, Anthea Lucrezia ; Galopin, Natacha ; Bejaud, Jérôme ; David, Stephanie ; Ballet, Caroline ; Benvegnu, Thierry ; Pecorari, Frédéric ; Chourpa, Igor ; Benoit, Jean-Pierre ; Passirani, Catherine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-e77ac912f786c88d8340d331d84650c3b764cf52740092e30c3e2a3f6b905dcc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Accumulation</topic><topic>animal models</topic><topic>Biomolecules</topic><topic>Blood plasma</topic><topic>Cancer</topic><topic>chemical bonding</topic><topic>Chemistry</topic><topic>confocal microscopy</topic><topic>Drug delivery systems</topic><topic>drugs</topic><topic>Energy transfer</topic><topic>Flow cytometry</topic><topic>Gene therapy</topic><topic>humans</topic><topic>image analysis</topic><topic>intravenous injection</topic><topic>Life Sciences</topic><topic>Lipids</topic><topic>Melanoma</topic><topic>metastasis</topic><topic>nanocapsules</topic><topic>nanocarriers</topic><topic>nanomedicine</topic><topic>Organs</topic><topic>Polyethylene glycol</topic><topic>polymers</topic><topic>Skin cancer</topic><topic>small interfering RNA</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Resnier, Pauline</creatorcontrib><creatorcontrib>Lepeltier, Elise</creatorcontrib><creatorcontrib>Emina, Anthea Lucrezia</creatorcontrib><creatorcontrib>Galopin, Natacha</creatorcontrib><creatorcontrib>Bejaud, Jérôme</creatorcontrib><creatorcontrib>David, Stephanie</creatorcontrib><creatorcontrib>Ballet, Caroline</creatorcontrib><creatorcontrib>Benvegnu, Thierry</creatorcontrib><creatorcontrib>Pecorari, Frédéric</creatorcontrib><creatorcontrib>Chourpa, Igor</creatorcontrib><creatorcontrib>Benoit, Jean-Pierre</creatorcontrib><creatorcontrib>Passirani, Catherine</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RSC advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Resnier, Pauline</au><au>Lepeltier, Elise</au><au>Emina, Anthea Lucrezia</au><au>Galopin, Natacha</au><au>Bejaud, Jérôme</au><au>David, Stephanie</au><au>Ballet, Caroline</au><au>Benvegnu, Thierry</au><au>Pecorari, Frédéric</au><au>Chourpa, Igor</au><au>Benoit, Jean-Pierre</au><au>Passirani, Catherine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Model Affitin and PEG modifications onto siRNA lipid nanocapsules: cell uptake and in vivo biodistribution improvements</atitle><jtitle>RSC advances</jtitle><addtitle>RSC Adv</addtitle><date>2019-08-30</date><risdate>2019</risdate><volume>9</volume><issue>47</issue><spage>27264</spage><epage>27278</epage><pages>27264-27278</pages><issn>2046-2069</issn><eissn>2046-2069</eissn><abstract>Malignant melanoma is an aggressive tumor, associated with the presence of local and/or distant metastases. The development of gene therapy by the use of small interfering RNA (siRNA) represents a promising new treatment. However, the protection of this biomolecule is necessary in order for it to be intravenously administrated, for example
its incorporation into nanomedicines. In parallel to the passive targeting usually obtained by pegylation, various studies have aimed at developing "smart" nanomedicines to efficiently deliver the drug to tumor sites. In this work, siRNA loaded lipid nanocapsules (LNCs) were modified with DSPE-polyethylene glycol (DSPE-PEG), tetraether-PEG (TE-PEG) and/or with an Affitin model, to assay multiple targeting strategies. The uptake of fluorescently labelled LNCs, nanocarrier integrity and siRNA release into human SK-Mel28 melanoma cells were studied by flow cytometry, conventional confocal microscopy and by confocal spectral imaging in a Förster Resonance Energy Transfer (FRET) mode. Surface modified siRNA LNCs were followed after human plasma incubation and after intravenous injection, in order to compare the stealth properties. Finally, the biodistribution of the different siRNA LNCs in healthy and melanoma tumor bearing mice models was assessed by
biofluorescence imaging (BFI), to evaluate the potential tumor targeting ability. The post-insertion of DSPE-PEG induced a strong decrease of the internalization into melanoma cells compared to TE-PEG modification. Both PEG polymer decorations induced a great plasma protection of siRNA but only DSPE-PEG led to stealth properties, even at low concentration (5 mM). The Affitin grafting by thiolation of DSPE-PEG was validated on siRNA LNCs. DSPE-PEG-Affitin LNCs were not detected in this melanoma tumor model but did not show unspecific accumulation in organs. DSPE-PEG and TE-PEG LNCs induced a significant intratumoral accumulation of modified LNCs.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>35529231</pmid><doi>10.1039/c9ra03668g</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-6024-7839</orcidid><orcidid>https://orcid.org/0000-0002-7666-6453</orcidid><orcidid>https://orcid.org/0000-0003-2116-0735</orcidid><orcidid>https://orcid.org/0000-0002-7854-0643</orcidid><orcidid>https://orcid.org/0000-0003-1613-9990</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central |
| subjects | Accumulation animal models Biomolecules Blood plasma Cancer chemical bonding Chemistry confocal microscopy Drug delivery systems drugs Energy transfer Flow cytometry Gene therapy humans image analysis intravenous injection Life Sciences Lipids Melanoma metastasis nanocapsules nanocarriers nanomedicine Organs Polyethylene glycol polymers Skin cancer small interfering RNA Tumors |
| title | Model Affitin and PEG modifications onto siRNA lipid nanocapsules: cell uptake and in vivo biodistribution improvements |
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