Targeted 8‑arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model
8-arm PEG (polyethylene-glycol) is a highly promising nanoplatform due to its small size (
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Veröffentlicht in: | ACS applied bio materials 2024-08, Vol.7 (8), p.5496-5505 |
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creator | McLean, Alan Zhang, Wei Cooke, Alexander Potter, Natalie S. Kopelman, Raoul Paulus, Yannis M. |
description | 8-arm PEG (polyethylene-glycol) is a highly promising nanoplatform due to its small size ( |
doi_str_mv | 10.1021/acsabm.4c00628 |
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This study evaluates 8-arm PEG uptake into cells (in vitro) and localization and clearance in vasculature (in vivo) for targeting of choroidal neovascularization in mice, an animal model of macular degeneration. 8-arm PEG nanoparticles were labeled with fluorescein isothiocyanate (FITC) and functionalized in the absence or presence of pentameric Ar-Gly-Asp (RGD; 4 RGD motifs and a PGC linker), one of the most common peptide motifs used for active targeting. In vitro studies show that RGD-conjugated 8-arm PEG nanoparticles exhibit enhanced cellular uptake relative to non-RGD-conjugated control NPs at 34% ± 9%. Laser-induced choroidal neovascularization (CNV) was performed in a mouse model to measure 8-arm PEG localization and clearance to model macular degeneration lesions in vivo. It was determined that both RGD-conjugated and non-RGD-conjugated (nRGD) 8-arm PEG particles localized to CNV lesions, with a half-life around 24 h. In vivo experiments showed that RGD-conjugated nanoparticles exhibited enhanced localization by 15–20% relative to without RGD controls. Exhibiting a high rate of localization and fast clearance relative to larger nanoparticles, targeted 8-arm PEG nanoparticles with a conjugated RGD-peptide could be a promising modality for macular degeneration diagnosis and therapy.</description><identifier>ISSN: 2576-6422</identifier><identifier>EISSN: 2576-6422</identifier><identifier>DOI: 10.1021/acsabm.4c00628</identifier><identifier>PMID: 39107259</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><ispartof>ACS applied bio materials, 2024-08, Vol.7 (8), p.5496-5505</ispartof><rights>2024 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a215t-2546438ed668b1a0d0a870dc8499a40243282c8da58d83cb5af69d6f65557a9f3</cites><orcidid>0000-0002-0615-628X ; 0000-0002-7226-7076 ; 0000-0002-7770-8272</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acsabm.4c00628$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acsabm.4c00628$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,777,781,2752,27057,27905,27906,56719,56769</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39107259$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McLean, Alan</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Cooke, Alexander</creatorcontrib><creatorcontrib>Potter, Natalie S.</creatorcontrib><creatorcontrib>Kopelman, Raoul</creatorcontrib><creatorcontrib>Paulus, Yannis M.</creatorcontrib><title>Targeted 8‑arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model</title><title>ACS applied bio materials</title><addtitle>ACS Appl. Bio Mater</addtitle><description>8-arm PEG (polyethylene-glycol) is a highly promising nanoplatform due to its small size (<10 nm), ease-of-conjugation (many functionalized variants are readily available with “click-like” properties), biocompatibility, and optical inactivity. This study evaluates 8-arm PEG uptake into cells (in vitro) and localization and clearance in vasculature (in vivo) for targeting of choroidal neovascularization in mice, an animal model of macular degeneration. 8-arm PEG nanoparticles were labeled with fluorescein isothiocyanate (FITC) and functionalized in the absence or presence of pentameric Ar-Gly-Asp (RGD; 4 RGD motifs and a PGC linker), one of the most common peptide motifs used for active targeting. In vitro studies show that RGD-conjugated 8-arm PEG nanoparticles exhibit enhanced cellular uptake relative to non-RGD-conjugated control NPs at 34% ± 9%. Laser-induced choroidal neovascularization (CNV) was performed in a mouse model to measure 8-arm PEG localization and clearance to model macular degeneration lesions in vivo. It was determined that both RGD-conjugated and non-RGD-conjugated (nRGD) 8-arm PEG particles localized to CNV lesions, with a half-life around 24 h. In vivo experiments showed that RGD-conjugated nanoparticles exhibited enhanced localization by 15–20% relative to without RGD controls. Exhibiting a high rate of localization and fast clearance relative to larger nanoparticles, targeted 8-arm PEG nanoparticles with a conjugated RGD-peptide could be a promising modality for macular degeneration diagnosis and therapy.</description><issn>2576-6422</issn><issn>2576-6422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kL1OwzAUhS0EolXpyog8IqQW24kdZ0SlFKRSGMoc3dhOSZXExU6QysQr8Io8CYGmiIXp_n3nSPcgdErJmBJGL0F5SMtxqAgRTB6gPuORGImQscM_fQ8NvV8TQhghAZXxMeoFMSUR43EfFUtwK1MbjeXn-we4Ej9OZ3gBlfVbX5vS48w6PLcKivwN6txW2GZ48mydzTUUeGHsK3jVFOD293v4GfG1WZnKuG5ptSlO0FEGhTfDrg7Q0810ObkdzR9md5Or-QgY5fWI8VCEgTRaCJlSIJqAjIhWMoxjCAkLAyaZkhq41DJQKYdMxFpkgnMeQZwFA3S-8904-9IYXydl7pUpCqiMbXwSEBnLSAZUtOh4hypnvXcmSzYuL8FtE0qS75CTXchJF3IrOOu8m7Q0-hffR9oCFzugFSZr27iqffU_ty_xcIf8</recordid><startdate>20240819</startdate><enddate>20240819</enddate><creator>McLean, Alan</creator><creator>Zhang, Wei</creator><creator>Cooke, Alexander</creator><creator>Potter, Natalie S.</creator><creator>Kopelman, Raoul</creator><creator>Paulus, Yannis M.</creator><general>American Chemical Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0615-628X</orcidid><orcidid>https://orcid.org/0000-0002-7226-7076</orcidid><orcidid>https://orcid.org/0000-0002-7770-8272</orcidid></search><sort><creationdate>20240819</creationdate><title>Targeted 8‑arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model</title><author>McLean, Alan ; Zhang, Wei ; Cooke, Alexander ; Potter, Natalie S. ; Kopelman, Raoul ; Paulus, Yannis M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a215t-2546438ed668b1a0d0a870dc8499a40243282c8da58d83cb5af69d6f65557a9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McLean, Alan</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Cooke, Alexander</creatorcontrib><creatorcontrib>Potter, Natalie S.</creatorcontrib><creatorcontrib>Kopelman, Raoul</creatorcontrib><creatorcontrib>Paulus, Yannis M.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>ACS applied bio materials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McLean, Alan</au><au>Zhang, Wei</au><au>Cooke, Alexander</au><au>Potter, Natalie S.</au><au>Kopelman, Raoul</au><au>Paulus, Yannis M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted 8‑arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model</atitle><jtitle>ACS applied bio materials</jtitle><addtitle>ACS Appl. Bio Mater</addtitle><date>2024-08-19</date><risdate>2024</risdate><volume>7</volume><issue>8</issue><spage>5496</spage><epage>5505</epage><pages>5496-5505</pages><issn>2576-6422</issn><eissn>2576-6422</eissn><abstract>8-arm PEG (polyethylene-glycol) is a highly promising nanoplatform due to its small size (<10 nm), ease-of-conjugation (many functionalized variants are readily available with “click-like” properties), biocompatibility, and optical inactivity. This study evaluates 8-arm PEG uptake into cells (in vitro) and localization and clearance in vasculature (in vivo) for targeting of choroidal neovascularization in mice, an animal model of macular degeneration. 8-arm PEG nanoparticles were labeled with fluorescein isothiocyanate (FITC) and functionalized in the absence or presence of pentameric Ar-Gly-Asp (RGD; 4 RGD motifs and a PGC linker), one of the most common peptide motifs used for active targeting. In vitro studies show that RGD-conjugated 8-arm PEG nanoparticles exhibit enhanced cellular uptake relative to non-RGD-conjugated control NPs at 34% ± 9%. Laser-induced choroidal neovascularization (CNV) was performed in a mouse model to measure 8-arm PEG localization and clearance to model macular degeneration lesions in vivo. It was determined that both RGD-conjugated and non-RGD-conjugated (nRGD) 8-arm PEG particles localized to CNV lesions, with a half-life around 24 h. In vivo experiments showed that RGD-conjugated nanoparticles exhibited enhanced localization by 15–20% relative to without RGD controls. Exhibiting a high rate of localization and fast clearance relative to larger nanoparticles, targeted 8-arm PEG nanoparticles with a conjugated RGD-peptide could be a promising modality for macular degeneration diagnosis and therapy.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>39107259</pmid><doi>10.1021/acsabm.4c00628</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0615-628X</orcidid><orcidid>https://orcid.org/0000-0002-7226-7076</orcidid><orcidid>https://orcid.org/0000-0002-7770-8272</orcidid></addata></record> |
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title | Targeted 8‑arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model |
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