Jeon Chanhee, Jun Hayoung, Kim Sooyeon, Song Nanhee, Yang Manseok, Lim Changjin, Lee Dongwon
Department of Bionanotechnology and Bioconvergence Engineering, Jeonbuk National University, Jeonju, Chonbuk 54896, Republic of Korea.
Department of Pharmacy, Jeonbuk National University, Jeonju, Chonbuk 54896, Republic of Korea.
ACS Appl Mater Interfaces. 2023 Feb 7. 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- retinoic acid (atRA) and hydroxybenzyl alcohol (HBA) simultaneously, in response to hydrogen peroxide (HO). Here, we report fucoidan-coated BORA-incorporated liposomes (f-BORALP) as clot-targeted antithrombotic liposomal nanomedicine with HO-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.
脂质体作为药物载体已得到广泛研究，但其临床应用却因药物负载量低和药物过早泄漏而受阻。据推测，可形成囊泡的前药能够以高摩尔分数掺入脂质双层，因此可作为治疗剂以及脂质体纳米药物中的结构成分。硼酸化视黄酸（BORA）作为一种前药被开发出来，它可以与常见脂质自组装形成高摩尔分数（40%）的脂质体，并在过氧化氢（HO）的作用下同时释放全反式维甲酸（atRA）和羟基苄醇（HBA）。在此，我们报道了岩藻依聚糖包被的含BORA脂质体（f-BORALP），它是一种针对血栓的抗血栓脂质体纳米药物，具有HO触发的多种治疗作用。在颈动脉血栓形成的小鼠模型中，f-BORALP优先在受损血管中积聚，并显著抑制血栓形成，证明了它们作为靶向抗血栓纳米药物的潜力。这项研究还为开发可形成囊泡和具有自毁性的前药以利用脂质体药物递送的优势提供了有价值的见解。
