UMMS Affiliation

Department of Radiology; New England Center for Stroke Research

Publication Date

2021-09-16

Document Type

Article

Disciplines

Biomedical Engineering and Bioengineering | Biophysics | Cardiovascular Diseases | Nervous System Diseases | Neurology | Neurosurgery | Radiology

Abstract

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.

Keywords

aneurysm targeting, cerebral aneurysm, glycoprotein VI (GPVI) coating, particle carriers, vascular models

Rights and Permissions

© 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.

DOI of Published Version

10.1002/btm2.10251

Source

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. Link to article on publisher's site

Journal/Book/Conference Title

Bioengineering and translational medicine

Related Resources

Link to Article in PubMed

PubMed ID

35079628

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Share

COinS