Transferrin-Conjugated SNALPs Encapsulating 2′-O-Methylated miR-34a for the Treatment of Multiple Myeloma
Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed. Wild type or completely 2′-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferri...
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| Veröffentlicht in: | BioMed research international 2014-01, Vol.2014 (2014), p.1-7 |
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| creator | Misso, Gabriella Tagliaferri, Pierosandro Tassone, Pierfrancesco Caraglia, Michele De Rosa, Giuseppe Scognamiglio, Immacolata Gallo Cantafio, Maria Eugenia Gullà, Annamaria Galeone, Aldo Di Martino, Maria Teresa Campani, Virginia Virgilio, Antonella |
| description | Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed. Wild type or completely 2′-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs. On the other hand, the chemical conjugation of SNALPs with Tf resulted in a significant decrease of the zeta potential, while size characteristics and miR-34a encapsulation into SNALPs were not significantly affected. In an experimental model of MM, all the animals treated with SNALPs encapsulating miR-34a showed a significant inhibition of the tumor growth. However, the use of SNALPs conjugated with Tf and encapsulating OMet miR-34a resulted in the highest increase of mice survival. These results may represent the proof of concept for the use of SNALPs encapsulating miR-34a for the treatment of MM. |
| doi_str_mv | 10.1155/2014/217365 |
| format | Article |
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Wild type or completely 2′-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs. On the other hand, the chemical conjugation of SNALPs with Tf resulted in a significant decrease of the zeta potential, while size characteristics and miR-34a encapsulation into SNALPs were not significantly affected. In an experimental model of MM, all the animals treated with SNALPs encapsulating miR-34a showed a significant inhibition of the tumor growth. However, the use of SNALPs conjugated with Tf and encapsulating OMet miR-34a resulted in the highest increase of mice survival. These results may represent the proof of concept for the use of SNALPs encapsulating miR-34a for the treatment of MM.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2014/217365</identifier><identifier>PMID: 24683542</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Puplishing Corporation</publisher><subject>Acids ; Animals ; Aqueous solutions ; Biomedical research ; Cancer ; Cell Proliferation ; Drug therapy ; Flow Cytometry ; Genetic aspects ; Humans ; Lipids ; Lipids - chemistry ; Male ; Medical research ; Methylation ; Mice, SCID ; MicroRNA ; MicroRNAs - metabolism ; Multiple myeloma ; Multiple Myeloma - therapy ; Nucleic Acids - chemistry ; Particle Size ; Physiological aspects ; Receptors, Transferrin - metabolism ; Static Electricity ; Studies ; Technological change ; Transferrin ; Transferrin - metabolism ; Tumors ; Unilamellar Liposomes - chemistry</subject><ispartof>BioMed research international, 2014-01, Vol.2014 (2014), p.1-7</ispartof><rights>Copyright © 2014 Immacolata Scognamiglio et al.</rights><rights>COPYRIGHT 2014 John Wiley & Sons, Inc.</rights><rights>Copyright © 2014 Immacolata Scognamiglio et al. Immacolata Scognamiglio et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2014 Immacolata Scognamiglio et al. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-dbec8a8e9b53768d95cc4b04f5c858aad96309429d734f5f874349dcb6634b423</citedby><cites>FETCH-LOGICAL-c527t-dbec8a8e9b53768d95cc4b04f5c858aad96309429d734f5f874349dcb6634b423</cites><orcidid>0000-0002-7787-2531 ; 0000-0002-1210-1269</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/PMC3943297/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943297/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24683542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Maiuri, Maria Chiara</contributor><creatorcontrib>Misso, Gabriella</creatorcontrib><creatorcontrib>Tagliaferri, Pierosandro</creatorcontrib><creatorcontrib>Tassone, Pierfrancesco</creatorcontrib><creatorcontrib>Caraglia, Michele</creatorcontrib><creatorcontrib>De Rosa, Giuseppe</creatorcontrib><creatorcontrib>Scognamiglio, Immacolata</creatorcontrib><creatorcontrib>Gallo Cantafio, Maria Eugenia</creatorcontrib><creatorcontrib>Gullà, Annamaria</creatorcontrib><creatorcontrib>Galeone, Aldo</creatorcontrib><creatorcontrib>Di Martino, Maria Teresa</creatorcontrib><creatorcontrib>Campani, Virginia</creatorcontrib><creatorcontrib>Virgilio, Antonella</creatorcontrib><title>Transferrin-Conjugated SNALPs Encapsulating 2′-O-Methylated miR-34a for the Treatment of Multiple Myeloma</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed. Wild type or completely 2′-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs. On the other hand, the chemical conjugation of SNALPs with Tf resulted in a significant decrease of the zeta potential, while size characteristics and miR-34a encapsulation into SNALPs were not significantly affected. In an experimental model of MM, all the animals treated with SNALPs encapsulating miR-34a showed a significant inhibition of the tumor growth. However, the use of SNALPs conjugated with Tf and encapsulating OMet miR-34a resulted in the highest increase of mice survival. 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Wild type or completely 2′-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs. On the other hand, the chemical conjugation of SNALPs with Tf resulted in a significant decrease of the zeta potential, while size characteristics and miR-34a encapsulation into SNALPs were not significantly affected. In an experimental model of MM, all the animals treated with SNALPs encapsulating miR-34a showed a significant inhibition of the tumor growth. However, the use of SNALPs conjugated with Tf and encapsulating OMet miR-34a resulted in the highest increase of mice survival. These results may represent the proof of concept for the use of SNALPs encapsulating miR-34a for the treatment of MM.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Puplishing Corporation</pub><pmid>24683542</pmid><doi>10.1155/2014/217365</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-7787-2531</orcidid><orcidid>https://orcid.org/0000-0002-1210-1269</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acids Animals Aqueous solutions Biomedical research Cancer Cell Proliferation Drug therapy Flow Cytometry Genetic aspects Humans Lipids Lipids - chemistry Male Medical research Methylation Mice, SCID MicroRNA MicroRNAs - metabolism Multiple myeloma Multiple Myeloma - therapy Nucleic Acids - chemistry Particle Size Physiological aspects Receptors, Transferrin - metabolism Static Electricity Studies Technological change Transferrin Transferrin - metabolism Tumors Unilamellar Liposomes - chemistry |
| title | Transferrin-Conjugated SNALPs Encapsulating 2′-O-Methylated miR-34a for the Treatment of Multiple Myeloma |
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