Enhancing the Stability and Immunomodulatory Activity of Liposomal Spherical Nucleic Acids through Lipid‐Tail DNA Modifications
Liposomal spherical nucleic acids (LSNAs) are an attractive therapeutic platform for gene regulation and immunomodulation due to their biocompatibility, chemically tunable structures, and ability to enter cells rapidly without the need for ancillary transfection agents. Such structures consist of sm...
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| Veröffentlicht in: | Small (Weinheim an der Bergstrasse, Germany) Germany), 2018-02, Vol.14 (5), p.n/a |
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| creator | Meckes, Brian Banga, Resham J. Nguyen, SonBinh T. Mirkin, Chad A. |
| description | Liposomal spherical nucleic acids (LSNAs) are an attractive therapeutic platform for gene regulation and immunomodulation due to their biocompatibility, chemically tunable structures, and ability to enter cells rapidly without the need for ancillary transfection agents. Such structures consist of small ( |
| doi_str_mv | 10.1002/smll.201702909 |
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Liposomal spherical nucleic acids synthesized by directly functionalizing DNA to lipids on the surface of a liposome leads to a higher DNA shell density and increased serum stability. These attributes lead to markedly increased cellular uptake and enhanced sequence‐specific immunostimulation.</description><identifier>ISSN: 1613-6810</identifier><identifier>EISSN: 1613-6829</identifier><identifier>DOI: 10.1002/smll.201702909</identifier><identifier>PMID: 29226611</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Adjuvants, Immunologic - chemistry ; Adjuvants, Immunologic - pharmacology ; Anchoring ; Biocompatibility ; Biological activity ; Biological properties ; biological stability ; Cell Line ; Cellular structure ; Cholesterol ; Deoxyribonucleic acid ; DNA ; DNA - chemistry ; Fluorescence ; FRET ; Gene expression ; Immune system ; immunomodulation ; Lipids ; Lipids - chemistry ; liposomal spherical nucleic acids ; Liposomes ; Nanotechnology ; Nucleic acids ; Nucleic Acids - chemistry ; Nucleic Acids - pharmacology ; Oligonucleotides ; Proteins ; Serum proteins ; SNA ; Transfection</subject><ispartof>Small (Weinheim an der Bergstrasse, Germany), 2018-02, Vol.14 (5), p.n/a</ispartof><rights>2017 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5059-91384a02425b95c935a9cb4e7c062fce072c9ae27fc06802e996b2a4b4da4e423</citedby><cites>FETCH-LOGICAL-c5059-91384a02425b95c935a9cb4e7c062fce072c9ae27fc06802e996b2a4b4da4e423</cites><orcidid>0000-0002-6634-7627 ; 0000-0002-8389-4622 ; 0000-0002-6977-3445</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fsmll.201702909$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fsmll.201702909$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29226611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meckes, Brian</creatorcontrib><creatorcontrib>Banga, Resham J.</creatorcontrib><creatorcontrib>Nguyen, SonBinh T.</creatorcontrib><creatorcontrib>Mirkin, Chad A.</creatorcontrib><title>Enhancing the Stability and Immunomodulatory Activity of Liposomal Spherical Nucleic Acids through Lipid‐Tail DNA Modifications</title><title>Small (Weinheim an der Bergstrasse, Germany)</title><addtitle>Small</addtitle><description>Liposomal spherical nucleic acids (LSNAs) are an attractive therapeutic platform for gene regulation and immunomodulation due to their biocompatibility, chemically tunable structures, and ability to enter cells rapidly without the need for ancillary transfection agents. Such structures consist of small (<100 nm) liposomal cores functionalized with a dense, highly oriented nucleic acid shell, both of which are key components in facilitating their biological activity. Here, the properties of LSNAs synthesized using conventional methods, anchoring cholesterol terminated oligonucleotides into a liposomal core, are compared to LSNAs made by directly modifying the surface of a liposomal core containing azide‐functionalized lipids with dibenzocyclooctyl‐terminated oligonucleotides. The surface densities of the oligonucleotides are measured for both types of LSNAs, with the lipid‐modified structures having approximately twice the oligonucleotide surface coverage. The stabilities and cellular uptake properties of these structures are also evaluated. The higher density, lipid‐functionalized structures are markedly more stable than conventional cholesterol‐based structures in the presence of other unmodified liposomes and serum proteins as evidenced by fluorescence assays. Significantly, this new form of LSNA exhibits more rapid cellular uptake and increased sequence‐specific toll‐like receptor activation in immune reporter cell lines, making it a promising candidate for immunotherapy.
Liposomal spherical nucleic acids synthesized by directly functionalizing DNA to lipids on the surface of a liposome leads to a higher DNA shell density and increased serum stability. These attributes lead to markedly increased cellular uptake and enhanced sequence‐specific immunostimulation.</description><subject>Adjuvants, Immunologic - chemistry</subject><subject>Adjuvants, Immunologic - pharmacology</subject><subject>Anchoring</subject><subject>Biocompatibility</subject><subject>Biological activity</subject><subject>Biological properties</subject><subject>biological stability</subject><subject>Cell Line</subject><subject>Cellular structure</subject><subject>Cholesterol</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - chemistry</subject><subject>Fluorescence</subject><subject>FRET</subject><subject>Gene expression</subject><subject>Immune system</subject><subject>immunomodulation</subject><subject>Lipids</subject><subject>Lipids - chemistry</subject><subject>liposomal spherical nucleic acids</subject><subject>Liposomes</subject><subject>Nanotechnology</subject><subject>Nucleic acids</subject><subject>Nucleic Acids - chemistry</subject><subject>Nucleic Acids - pharmacology</subject><subject>Oligonucleotides</subject><subject>Proteins</subject><subject>Serum proteins</subject><subject>SNA</subject><subject>Transfection</subject><issn>1613-6810</issn><issn>1613-6829</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQhy0EoqVw5YgsceGyy9ixk_iCtCoFKqXlsOVsOY6zceXYi50U7Q3egGfkSfBqy_LnwskjzzefZvRD6DmBJQGgr9Po3JICqYAKEA_QKSlJsShrKh4eawIn6ElKtwAFoax6jE6ooLQsCTlF3y78oLy2foOnweD1pFrr7LTDynf4chxnH8bQzU5NIe7wSk_2bt8NPW7sNqQwKofX28FEq3N1PWtnrM6c7VIWxjBvhj1pux9fv98o6_Db6xW-Cp3t88Bkg09P0aNeuWSe3b9n6NO7i5vzD4vm4_vL81Wz0By4WAhS1EwBZZS3gmtRcCV0y0yloaS9NlBRLZShVZ8_aqBGiLKlirWsU8wwWpyhNwfvdm5H02njp6ic3EY7qriTQVn5d8fbQW7CneQ14TVnWfDqXhDD59mkSY42aeOc8ibMSRJRcS4YgzqjL_9Bb8McfT4vU6IAShjhmVoeKB1DStH0x2UIyH26cp-uPKabB178ecIR_xVnBsQB-GKd2f1HJ9dXTfNb_hNkK7S4</recordid><startdate>20180201</startdate><enddate>20180201</enddate><creator>Meckes, Brian</creator><creator>Banga, Resham J.</creator><creator>Nguyen, SonBinh T.</creator><creator>Mirkin, Chad A.</creator><general>Wiley Subscription Services, Inc</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>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6634-7627</orcidid><orcidid>https://orcid.org/0000-0002-8389-4622</orcidid><orcidid>https://orcid.org/0000-0002-6977-3445</orcidid></search><sort><creationdate>20180201</creationdate><title>Enhancing the Stability and Immunomodulatory Activity of Liposomal Spherical Nucleic Acids through Lipid‐Tail DNA Modifications</title><author>Meckes, Brian ; Banga, Resham J. ; Nguyen, SonBinh T. ; Mirkin, Chad A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5059-91384a02425b95c935a9cb4e7c062fce072c9ae27fc06802e996b2a4b4da4e423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adjuvants, Immunologic - chemistry</topic><topic>Adjuvants, Immunologic - pharmacology</topic><topic>Anchoring</topic><topic>Biocompatibility</topic><topic>Biological activity</topic><topic>Biological properties</topic><topic>biological stability</topic><topic>Cell Line</topic><topic>Cellular structure</topic><topic>Cholesterol</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - chemistry</topic><topic>Fluorescence</topic><topic>FRET</topic><topic>Gene expression</topic><topic>Immune system</topic><topic>immunomodulation</topic><topic>Lipids</topic><topic>Lipids - chemistry</topic><topic>liposomal spherical nucleic acids</topic><topic>Liposomes</topic><topic>Nanotechnology</topic><topic>Nucleic acids</topic><topic>Nucleic Acids - chemistry</topic><topic>Nucleic Acids - pharmacology</topic><topic>Oligonucleotides</topic><topic>Proteins</topic><topic>Serum proteins</topic><topic>SNA</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meckes, Brian</creatorcontrib><creatorcontrib>Banga, Resham J.</creatorcontrib><creatorcontrib>Nguyen, SonBinh T.</creatorcontrib><creatorcontrib>Mirkin, Chad A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Small (Weinheim an der Bergstrasse, Germany)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meckes, Brian</au><au>Banga, Resham J.</au><au>Nguyen, SonBinh T.</au><au>Mirkin, Chad A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhancing the Stability and Immunomodulatory Activity of Liposomal Spherical Nucleic Acids through Lipid‐Tail DNA Modifications</atitle><jtitle>Small (Weinheim an der Bergstrasse, Germany)</jtitle><addtitle>Small</addtitle><date>2018-02-01</date><risdate>2018</risdate><volume>14</volume><issue>5</issue><epage>n/a</epage><issn>1613-6810</issn><eissn>1613-6829</eissn><abstract>Liposomal spherical nucleic acids (LSNAs) are an attractive therapeutic platform for gene regulation and immunomodulation due to their biocompatibility, chemically tunable structures, and ability to enter cells rapidly without the need for ancillary transfection agents. Such structures consist of small (<100 nm) liposomal cores functionalized with a dense, highly oriented nucleic acid shell, both of which are key components in facilitating their biological activity. Here, the properties of LSNAs synthesized using conventional methods, anchoring cholesterol terminated oligonucleotides into a liposomal core, are compared to LSNAs made by directly modifying the surface of a liposomal core containing azide‐functionalized lipids with dibenzocyclooctyl‐terminated oligonucleotides. The surface densities of the oligonucleotides are measured for both types of LSNAs, with the lipid‐modified structures having approximately twice the oligonucleotide surface coverage. The stabilities and cellular uptake properties of these structures are also evaluated. The higher density, lipid‐functionalized structures are markedly more stable than conventional cholesterol‐based structures in the presence of other unmodified liposomes and serum proteins as evidenced by fluorescence assays. Significantly, this new form of LSNA exhibits more rapid cellular uptake and increased sequence‐specific toll‐like receptor activation in immune reporter cell lines, making it a promising candidate for immunotherapy.
Liposomal spherical nucleic acids synthesized by directly functionalizing DNA to lipids on the surface of a liposome leads to a higher DNA shell density and increased serum stability. These attributes lead to markedly increased cellular uptake and enhanced sequence‐specific immunostimulation.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29226611</pmid><doi>10.1002/smll.201702909</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6634-7627</orcidid><orcidid>https://orcid.org/0000-0002-8389-4622</orcidid><orcidid>https://orcid.org/0000-0002-6977-3445</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adjuvants, Immunologic - chemistry Adjuvants, Immunologic - pharmacology Anchoring Biocompatibility Biological activity Biological properties biological stability Cell Line Cellular structure Cholesterol Deoxyribonucleic acid DNA DNA - chemistry Fluorescence FRET Gene expression Immune system immunomodulation Lipids Lipids - chemistry liposomal spherical nucleic acids Liposomes Nanotechnology Nucleic acids Nucleic Acids - chemistry Nucleic Acids - pharmacology Oligonucleotides Proteins Serum proteins SNA Transfection |
| title | Enhancing the Stability and Immunomodulatory Activity of Liposomal Spherical Nucleic Acids through Lipid‐Tail DNA Modifications |
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