Clot-Targeted Antithrombotic Liposomal Nanomedicine Containing High Content of H2O2‑Activatable Hybrid Prodrugs

• Published in: ACS applied materials & interfaces Vol. 15; no. 7; pp. 8999 - 9009
• Main Authors: Jeon, Chanhee, Jun, Hayoung, Kim, Sooyeon, Song, Nanhee, Yang, Manseok, Lim, Changjin, Lee, Dongwon
• Format: Journal Article
• Language: English
• Published: American Chemical Society 22.02.2023
• Subjects: Biological and Medical Applications of Materials and Interfaces; retinoic acid; antithrombotic drug; thrombus; hybrid prodrug; liposome
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.2c20750

Liposomes have been extensively explored as drug carriers, but their clinical translation has been hampered by their low drug-loading content and premature leakage of drug payloads. It was reasoned that vesicle-forming prodrugs could be incorporated into the lipid bilayer at a high molar fraction and therefore serve as a therapeutic agent as well as a structural component in liposomal nanomedicine. Boronated retinoic acid (BORA) was developed as a prodrug, which can self-assemble with common lipids to form liposomes at a high molar fraction (40%) and release all-trans retinoic acid (atRA) and hydroxybenzyl alcohol (HBA) simultaneously, in response to hydrogen peroxide (H2O2). Here, we report fucoidan-coated BORA-incorporated liposomes (f-BORALP) as clot-targeted antithrombotic liposomal nanomedicine with H2O2-triggered multiple therapeutic actions. In the mouse model of carotid arterial thrombosis, f-BORALP preferentially accumulated in the injured blood vessel and significantly suppressed thrombus formation, demonstrating their potential as targeted antithrombotic nanomedicine. This study also provides valuable insight into the development of vesicle-forming and self-immolative prodrugs to exploit the benefits of liposomal drug delivery.