Photothrombolytics: A light-driven technology for the targeted lysis of thrombi

Basanta Acharya; Caylie A McGlade; Haifeng Yin; Tomohiro Kawano; Lauren Haar; Nigel Mackman; Rani S Sellers; Xianming Tan; Aadra P Bhatt; David S Lawrence; Brianna M Vickerman

doi:10.1016/j.jconrel.2024.11.059

Photothrombolytics: A light-driven technology for the targeted lysis of thrombi

J Control Release. 2024 Dec 17:378:281-293. doi: 10.1016/j.jconrel.2024.11.059. Online ahead of print.

Authors

Affiliations

¹ Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
² Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
³ McAllister Heart Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
⁴ Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
⁵ Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
⁶ Department of Biostatistics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
⁷ Division of Gastroenterology & Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
⁸ Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
⁹ Eshelman Innovation, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: brianna.vickerman@unc.edu.

PMID: 39615753
DOI: 10.1016/j.jconrel.2024.11.059

Abstract

Occlusive blood clots remain a significant global health challenge and result in emergencies that are main causes of death and disability worldwide. Thrombolytic agents (including tissue plasminogen activator, tPA) are the only pharmacological means to dissolve blood clots. However, these drugs have modest efficacy and severe safety concerns persist. We have developed light-responsive tPA-loaded red blood cells (tPA-RBCs^Photo) to target thrombolytic activity at the site of a blood clot. Herein, we describe the use of light to control the release of tPA from engineered RBCs and the subsequent degradation of a blood clot ex vivo. Furthermore, we have employed this technology to restore blood flow to an occluded mouse artery in vivo using a targeted dose that is 25 times lower than conventional systemic tPA treatment.

Keywords: Biological carriers; Drug delivery; Phototherapeutics; Thrombolytics.

Published by Elsevier B.V.