Near-infrared light-responsive liposomes for protein delivery: Towards bleeding-free photothermally-assisted thrombolysis

Ahmed Refaat; Blanca Del Rosal; Jathushan Palasubramaniam; Geoffrey Pietersz; Xiaowei Wang; Simon E Moulton; Karlheinz Peter

doi:10.1016/j.jconrel.2021.07.024

Near-infrared light-responsive liposomes for protein delivery: Towards bleeding-free photothermally-assisted thrombolysis

J Control Release. 2021 Sep 10:337:212-223. doi: 10.1016/j.jconrel.2021.07.024. Epub 2021 Jul 18.

Authors

Ahmed Refaat¹, Blanca Del Rosal², Jathushan Palasubramaniam³, Geoffrey Pietersz⁴, Xiaowei Wang⁵, Simon E Moulton⁶, Karlheinz Peter⁷

Affiliations

¹ Department of Telecommunications, Electrical, Robotics and Biomedical Engineering, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Melbourne, VIC 3122, Australia; Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Molecular Imaging and Theranostics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Pharmaceutics Department, Faculty of Pharmacy, Alexandria University, 21021, Egypt.
² ARC Centre of Excellence for Nanoscale BioPhotonics, School of Science, RMIT University, Melbourne, VIC 3000, Australia.
³ Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Molecular Imaging and Theranostics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Department of Medicine, Monash University, Melbourne, VIC 3800, Australia; Department of Cardiology, Alfred Hospital, Melbourne, VIC 3004, Australia.
⁴ Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Burnet Institute, Melbourne, VIC 3004, Australia.
⁵ Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Molecular Imaging and Theranostics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Department of Medicine, Monash University, Melbourne, VIC 3800, Australia; Department of Cardiometabolic Health, University of Melbourne, VIC 3010, Australia.
⁶ Department of Telecommunications, Electrical, Robotics and Biomedical Engineering, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Melbourne, VIC 3122, Australia; Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, VIC 3122, Australia; ARC Centre of Excellence for Electromaterials Science, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Melbourne, VIC 3122, Australia; Aikenhead Centre for Medical Discovery (ACMD), St Vincent's Hospital, Melbourne, VIC 3065, Australia; Australian Institute for Innovative Materials, Intelligent Polymer Research Institute, University of Wollongong, Wollongong, NSW 2500, Australia. Electronic address: [email protected].
⁷ Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Department of Medicine, Monash University, Melbourne, VIC 3800, Australia; Department of Cardiology, Alfred Hospital, Melbourne, VIC 3004, Australia; Department of Cardiometabolic Health, University of Melbourne, VIC 3010, Australia. Electronic address: [email protected].

PMID: 34284049
DOI: 10.1016/j.jconrel.2021.07.024

Abstract

Smart drug delivery systems represent state-of-the-art approaches for targeted therapy of life-threatening diseases such as cancer and cardiovascular diseases. Stimuli-responsive on-demand release of therapeutic agents at the diseased site can significantly limit serious adverse effects. In this study, we engineered a near-infrared (NIR) light-responsive liposomal gold nanorod-containing platform for on-demand delivery of proteins using a hybrid formulation of ultrasmall gold nanorods (AuNRs), thermosensitive phospholipid (DPPC) and non-ionic surfactant (Brij58). In light-triggered release optimization studies, 55.6% (± 4.8) of a FITC-labelled model protein, ovalbumin (MW 45 kDa) was released in 15 min upon NIR irradiation (785 nm, 1.35 W/cm² for 5 min). This platform was then utilized to test on-demand delivery of urokinase-plasminogen activator (uPA) for bleeding-free photothermally-assisted thrombolysis, where the photothermal effect of AuNRs would synergize with the released uPA in clot lysis. Urokinase light-responsive liposomes showed 80.7% (± 4.5) lysis of an in vitro halo-clot model in 30 min following NIR irradiation (785 nm, 1.35 W/cm² for 5 min) compared to 36.3% (± 4.4) and 15.5% (± 5.5) clot lysis from equivalent free uPA and non-irradiated liposomes respectively. These results show the potential of low-dose, site-specific thrombolysis via the combination of light-triggered delivery/release of uPA from liposomes combined with photothermal thrombolytic effects from gold nanorods. In conclusion, newly engineered, gold nanorod-based, NIR light-responsive liposomes represent a promising drug delivery system for site-directed, photothermally-stimulated therapeutic protein release.

Keywords: Drug release; Gold nanorods; Light-responsive liposomes; Photothermally-assisted thrombolysis; Urokinase liposomes; uPA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Doxorubicin*
Drug Delivery Systems
Gold
Infrared Rays
Liposomes*
Thrombolytic Therapy

Substances

Liposomes
Gold
Doxorubicin