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dc.contributor.authorEpshtein, Mark
dc.contributor.authorLevi, Moran
dc.contributor.authorKraitem, Afif M.
dc.contributor.authorZidan, Hikaia
dc.contributor.authorKing, Robert M.
dc.contributor.authorGawaz, Meinrad
dc.contributor.authorGounis, Matthew J.
dc.contributor.authorKorin, Netanel
dc.date2022-08-11T08:10:06.000
dc.date.accessioned2022-08-23T16:55:16Z
dc.date.available2022-08-23T16:55:16Z
dc.date.issued2021-09-16
dc.date.submitted2022-04-21
dc.identifier.citation<p>Epshtein M, Levi M, Kraitem AM, Zidan H, King RM, Gawaz M, Gounis MJ, Korin N. Biophysical targeting of high-risk cerebral aneurysms. Bioeng Transl Med. 2021 Sep 16;7(1):e10251. doi: 10.1002/btm2.10251. PMID: 35079628; PMCID: PMC8780020. <a href="https://doi.org/10.1002/btm2.10251">Link to article on publisher's site</a></p>
dc.identifier.issn2380-6761 (Linking)
dc.identifier.doi10.1002/btm2.10251
dc.identifier.pmid35079628
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42679
dc.description.abstractLocalized delivery of diagnostic/therapeutic agents to cerebral aneurysms, lesions in brain arteries, may offer a new treatment paradigm. Since aneurysm rupture leading to subarachnoid hemorrhage is a devastating medical emergency with high mortality, the ability to noninvasively diagnose high-risk aneurysms is of paramount importance. Moreover, treatment of unruptured aneurysms with invasive surgery or minimally invasive neurointerventional surgery poses relatively high risk and there is presently no medical treatment of aneurysms. Here, leveraging the endogenous biophysical properties of brain aneurysms, we develop particulate carriers designed to localize in aneurysm low-shear flows as well as to adhere to a diseased vessel wall, a known characteristic of high-risk aneurysms. We first show, in an in vitro model, flow guided targeting to aneurysms using micron-sized (2 mum) particles, that exhibited enhanced targeting ( > 7 folds) to the aneurysm cavity while smaller nanoparticles (200 nm) showed no preferable accumulation. We then functionalize the microparticles with glycoprotein VI (GPVI), the main platelet receptor for collagen under low-medium shear, and study their targeting in an in vitro reconstructed patient-specific aneurysm that contained a disrupted endothelium at the cavity. Results in this model showed that GPVI microparticles localize at the injured aneurysm an order of magnitude ( > 9 folds) more than control particles. Finally, effective targeting to aneurysm sites was also demonstrated in an in vivo rabbit aneurysm model with a disrupted endothelium. Altogether, the presented biophysical strategy for targeted delivery may offer new treatment opportunities for cerebral aneurysms.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=35079628&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectaneurysm targeting
dc.subjectcerebral aneurysm
dc.subjectglycoprotein VI (GPVI) coating
dc.subjectparticle carriers
dc.subjectvascular models
dc.subjectBiomedical Engineering and Bioengineering
dc.subjectBiophysics
dc.subjectCardiovascular Diseases
dc.subjectNervous System Diseases
dc.subjectNeurology
dc.subjectNeurosurgery
dc.subjectRadiology
dc.titleBiophysical targeting of high-risk cerebral aneurysms
dc.typeJournal Article
dc.source.journaltitleBioengineering and translational medicine
dc.source.volume7
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5957&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4923
dc.identifier.contextkey28760673
refterms.dateFOA2022-08-23T16:55:16Z
html.description.abstract<p>Localized delivery of diagnostic/therapeutic agents to cerebral aneurysms, lesions in brain arteries, may offer a new treatment paradigm. Since aneurysm rupture leading to subarachnoid hemorrhage is a devastating medical emergency with high mortality, the ability to noninvasively diagnose high-risk aneurysms is of paramount importance. Moreover, treatment of unruptured aneurysms with invasive surgery or minimally invasive neurointerventional surgery poses relatively high risk and there is presently no medical treatment of aneurysms. Here, leveraging the endogenous biophysical properties of brain aneurysms, we develop particulate carriers designed to localize in aneurysm low-shear flows as well as to adhere to a diseased vessel wall, a known characteristic of high-risk aneurysms. We first show, in an in vitro model, flow guided targeting to aneurysms using micron-sized (2 mum) particles, that exhibited enhanced targeting ( > 7 folds) to the aneurysm cavity while smaller nanoparticles (200 nm) showed no preferable accumulation. We then functionalize the microparticles with glycoprotein VI (GPVI), the main platelet receptor for collagen under low-medium shear, and study their targeting in an in vitro reconstructed patient-specific aneurysm that contained a disrupted endothelium at the cavity. Results in this model showed that GPVI microparticles localize at the injured aneurysm an order of magnitude ( > 9 folds) more than control particles. Finally, effective targeting to aneurysm sites was also demonstrated in an in vivo rabbit aneurysm model with a disrupted endothelium. Altogether, the presented biophysical strategy for targeted delivery may offer new treatment opportunities for cerebral aneurysms.</p>
dc.identifier.submissionpathoapubs/4923
dc.contributor.departmentNew England Center for Stroke Research
dc.contributor.departmentDepartment of Radiology
dc.source.pagese10251


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© 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as © 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.