journal article·2023-01Open access

Activated Platelet‐Targeted IR780 Immunoliposomes for Photothermal Thrombolysis

Ahmed Refaat, Blanca del Rosal, Viktoria Bongcaron, Aidan P. G. Walsh, Geoffrey Pietersz, Karlheinz Peter, Simon E. Moulton, Xiaowei Wang

Advanced Functional Materials· Volume 33· Issue 4

Abstract

Abstract Acute thrombosis is a leading cause of mortality and morbidity worldwide. Pharmacological thrombolysis relies on plasminogen activators (PAs), which are associated with major side effects including potentially fatal bleeding. Alternative therapeutic options that do not rely on PAs are urgently required. Here, the efficacy of targeted photothermal therapy is evaluated for thrombolysis using liposomes loaded with IR780 dye, which release heat upon near‐infrared (NIR) irradiation. Liposomes targeted to activated platelets—one of the main components of thrombi—accumulate preferentially in thrombi both in vitro and in vivo compared to non‐targeted controls. In a mouse model of thrombosis, targeted IR780 immunoliposomes (Tar‐IR‐L) produce ≈12 °C average local temperature increase upon NIR irradiation (5 min, 1 W cm−2). This causes a significant reduction in clot area compared to controls treated with non‐targeted liposomes or phosphate‐buffered saline, which only increase local temperature slightly (6 and 3 °C) when irradiated. Co‐loading a low‐dose single chain urokinase plasminogen activator (scuPA) to targeted IR780 liposomes (Tar‐scuPA‐IR‐L) does not result in a superior thrombolytic effect, which indicates that photothermal therapy alone may allow thrombolysis without the need for fibrinolytic drugs. This approach may prevent potential bleeding complications, promising a safer alternative to current pharmacological approaches.
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Research context

OpenAlex topics: Venous Thromboembolism Diagnosis and Management · Protease and Inhibitor Mechanisms · Blood Coagulation and Thrombosis Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Engineering Technologies Swinburne University of Technology John St Melbourne Victoria 3122 Australia

Atherothrombosis and Vascular Biology Laboratory Baker Heart and Diabetes Institute 75 Commercial Road Melbourne Victoria 3004 Australia

Molecular Imaging and Theranostics Laboratory Baker Heart and Diabetes Institute 75 Commercial Road Melbourne Victoria 3004 Australia

Pharmaceutics Department Faculty of Pharmacy Alexandria University 1 El‐Khartoum Square Azarita 21021 Egypt

School of Science RMIT University 124 La Trobe St Melbourne Victoria 3000 Australia

Department of Medicine Monash University 27 Rainforest Walk Melbourne Victoria 3800 Australia

Department of Cardiometabolic Health University of Melbourne Grattan St Parkville Victoria 3010 Australia

Burnet Institute 85 Commercial Road Melbourne Victoria 3004 Australia

Department of Cardiovascular Research Translation, and Implementation La Trobe University Plenty Rd & Kingsbury Dr Bundoora Melbourne Victoria 3083 Australia

Department of Cardiology Alfred Hospital 55 Commercial Road Melbourne Victoria 3004 Australia

Aikenhead Centre for Medical Discovery (ACMD) St Vincent's Hospital 41 Victoria Parade, Fitzroy Melbourne Victoria 3065 Australia

Iverson Health Innovation Research Institute Swinburne University of Technology John St Melbourne Victoria 3122 Australia

Australian Institute for Innovative Materials Intelligent Polymer Research Institute University of Wollongong Northfields Ave Wollongong New South Wales 2500 Australia

Funding

Australian Research Council · RMIT University · Monash University · Swinburne University of Technology · Baker IDI Heart and Diabetes Institute

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