OC 17.4 - Engineering hyperechogenic colloids with thrombus-targeting capabilities from platelet membranes

Sunday, June 23, 2024

10:15 – 10:30 ICT

Room: 210 A-D

Presenting Author(s)

Mitchell J. Moon

Research Officer
Baker Heart and Diabetes Institute
Melbourne, Victoria, Australia

Co-Author(s)

MV

Mark Vidallon

Research Officer
Baker Heart and Diabetes Institute
Melbourne, Victoria, Australia
HL

Haikun Liu

PhD Student
Baker Heart and Diabetes Institute
Melbourne, Victoria, Australia
YS

Yuyang Song

PhD Student
Baker Heart and Diabetes Institute
Melbourne, Victoria, Australia
SC

Simon Crawford

Technical Staff
Monash University
Melbourne, Victoria, Australia
BT

Boon Teo

Research Associate
Monash University
Melbourne, Victoria, Australia
JM

James D. McFadyen

Group Leader
Baker Heart and Diabetes Insitute
Melbourne, Victoria, Australia
AB

Alexis Bishop

Lecturer
Monash University
Melbourne, Victoria, Australia
RT

Rico Tabor

Laboratory Head
Monash University
Melbourne, Victoria, Australia
KP

Karlheinz Peter

Laboratory Head
Baker Heart and Diabetes Institute
Melbourne, Victoria, Australia
XW

Xiaowei Wang

Laboratory Head
Baker Heart and Diabetes Institute
Melbourne, Victoria, Australia

Background: Thrombosis-related cardiovascular diseases remain the leading global cause of mortality and morbidity. Despite this, pharmacological treatment options and direct visualisation diagnostic tools remain limited. In this study, we present a nanobiotechnology approach with a focus on clinical translation, aimed at advancing early diagnosis and enhancing treatment options for thrombotic disorders.

Aims: We aim to develop novel thrombus-targeted, acoustically active particles derived from human platelet membranes for diagnostic imaging and as potential thrombolytic drug nanocarriers.

Methods: Isolated platelet membranes were dispersed in a glycerol-PBS mixture in a tube containing a perfluorohexane-air mixture. Platelet Membrane-Derived Bubbles (PMBs) were fabricated by sonication at the gas-liquid interface to induce acoustic cavitation of gas bubbles into the platelet membrane.

Results: PMBs exhibit distinctive characteristics compared to conventional nanoparticles. These PMBs possess an average diameter of 700 nm and a negative ζ-potential, mirroring the attributes of parent platelet membranes. Utilizing diagnostic ultrasound imaging, we demonstrated the ability to visualize PMBs as hyperechogenic entities in agarose phantoms in vitro and in live mice in vivo. Furthermore, through confocal laser microscopy, we verified the retention of crucial transmembrane proteins, such as CD41 (GPIIb) and CD42 (GPIb), pivotal in conferring platelet-specific targeting functions. Importantly, our platelet aggregation studies confirmed that PMBs do not induce platelet aggregation but instead adhere to preformed platelet-rich in vitro thrombi. Overall, our work showcases the safe and precise utilization of PMBs to directly target acute thrombosis induced by laser injury in murine mesenteric veins in vivo, as visualized through intravital microscopy.

Conclusion(s): In conclusion, we have successfully developed a rapid method for generating PMBs with unique ultrasound-directed and thrombus-targeting properties. These exceptional attributes of PMBs hold significant promise for advancing the field of ultrasound diagnostic thrombus imaging and clot-targeted therapy in the clinical context.