Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy
Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic co...
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| Veröffentlicht in: | PloS one 2016-04, Vol.11 (4), p.e0154437 |
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| creator | Guo, Yan Johnson, Mary A Mehrabian, Zara Mishra, Manoj K Kannan, Rangaramanujam Miller, Neil R Bernstein, Steven L |
| description | Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment.
NAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION.
Following NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats.
Dendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia. |
| doi_str_mv | 10.1371/journal.pone.0154437 |
| format | Article |
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NAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION.
Following NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats.
Dendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0154437</identifier><identifier>PMID: 27128315</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animals ; Astrocytes ; Astrocytes - metabolism ; Astrocytes - pathology ; Bioaccumulation ; Bioactive compounds ; Biological activity ; Biology and Life Sciences ; Carbocyanines - chemistry ; Carbocyanines - metabolism ; Care and treatment ; Chemical compounds ; Controlled release ; Dendrimers ; Dendrimers - chemical synthesis ; Dendrimers - pharmacokinetics ; Disease Models, Animal ; Drug Carriers - chemical synthesis ; Drug Carriers - pharmacokinetics ; Fluorescence ; Fluorescent Dyes - chemistry ; Fluorescent Dyes - metabolism ; Fluorescent indicators ; Humans ; I.R. radiation ; Inflammation ; Injections, Intravenous ; Intravitreal Injections ; Iodine ; Ischemia ; Laboratory animals ; Lesions ; Localization ; Macaca mulatta ; Macrophages ; Macrophages - metabolism ; Macrophages - pathology ; Male ; Medical research ; Medicine ; Medicine and Health Sciences ; Molecular Targeted Therapy ; Nanoparticles ; Nanoparticles - chemistry ; Nanoparticles - metabolism ; Neuropathy ; Neurosciences ; Optic nerve ; Optic Nerve - metabolism ; Optic Nerve - pathology ; Optic neuropathy ; Optic Neuropathy, Ischemic - metabolism ; Optic Neuropathy, Ischemic - pathology ; Particle Size ; Pharmacology ; Polyamines - chemistry ; Polymers ; Rats ; Rats, Long-Evans ; Retina ; Rodents ; Sustained release</subject><ispartof>PloS one, 2016-04, Vol.11 (4), p.e0154437</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Guo et al 2016 Guo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-43492276034e86e74619d921c8d2f74392d37c70ab5220f8e3813e4cb01073793</citedby><cites>FETCH-LOGICAL-c692t-43492276034e86e74619d921c8d2f74392d37c70ab5220f8e3813e4cb01073793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851377/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851377/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27128315$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chidlow, Glyn</contributor><creatorcontrib>Guo, Yan</creatorcontrib><creatorcontrib>Johnson, Mary A</creatorcontrib><creatorcontrib>Mehrabian, Zara</creatorcontrib><creatorcontrib>Mishra, Manoj K</creatorcontrib><creatorcontrib>Kannan, Rangaramanujam</creatorcontrib><creatorcontrib>Miller, Neil R</creatorcontrib><creatorcontrib>Bernstein, Steven L</creatorcontrib><title>Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment.
NAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION.
Following NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats.
Dendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. 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These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment.
NAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION.
Following NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats.
Dendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27128315</pmid><doi>10.1371/journal.pone.0154437</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1785489688 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animal models Animals Astrocytes Astrocytes - metabolism Astrocytes - pathology Bioaccumulation Bioactive compounds Biological activity Biology and Life Sciences Carbocyanines - chemistry Carbocyanines - metabolism Care and treatment Chemical compounds Controlled release Dendrimers Dendrimers - chemical synthesis Dendrimers - pharmacokinetics Disease Models, Animal Drug Carriers - chemical synthesis Drug Carriers - pharmacokinetics Fluorescence Fluorescent Dyes - chemistry Fluorescent Dyes - metabolism Fluorescent indicators Humans I.R. radiation Inflammation Injections, Intravenous Intravitreal Injections Iodine Ischemia Laboratory animals Lesions Localization Macaca mulatta Macrophages Macrophages - metabolism Macrophages - pathology Male Medical research Medicine Medicine and Health Sciences Molecular Targeted Therapy Nanoparticles Nanoparticles - chemistry Nanoparticles - metabolism Neuropathy Neurosciences Optic nerve Optic Nerve - metabolism Optic Nerve - pathology Optic neuropathy Optic Neuropathy, Ischemic - metabolism Optic Neuropathy, Ischemic - pathology Particle Size Pharmacology Polyamines - chemistry Polymers Rats Rats, Long-Evans Retina Rodents Sustained release |
| title | Dendrimers Target the Ischemic Lesion in Rodent and Primate Models of Nonarteritic Anterior Ischemic Optic Neuropathy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T02%3A06%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Dendrimers%20Target%20the%20Ischemic%20Lesion%20in%20Rodent%20and%20Primate%20Models%20of%20Nonarteritic%20Anterior%20Ischemic%20Optic%20Neuropathy&rft.jtitle=PloS%20one&rft.au=Guo,%20Yan&rft.date=2016-04-29&rft.volume=11&rft.issue=4&rft.spage=e0154437&rft.pages=e0154437-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0154437&rft_dat=%3Cgale_plos_%3EA453417999%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1785489688&rft_id=info:pmid/27128315&rft_galeid=A453417999&rft_doaj_id=oai_doaj_org_article_e4de9d623e0e4d65a1be9c3ce6089ca9&rfr_iscdi=true |