Document Type
Article
Publication Date
2-28-2026
Abstract
Thrombosis remains a leading cause of cardiovascular morbidity and mortality. During thrombosis, activated platelets and endothelial cells expose phosphatidylserine (PS) on their outer membranes, creating a surface that accelerates clot formation. Current antithrombotic therapies, such as heparin and warfarin, carry significant bleeding risks, highlighting the need for safer alternatives. In response, we developed a PS-targeting liposomal formulation composed of Zn-dipicolylamine (DPA)-cyanine-3[22,22] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (molar ratio 3:97). This DPA-harboring liposome (DPAL) binds selectively to PS-rich surfaces such as activated platelets and has demonstrated efficacy in reducing thrombosis in mouse models, with minimal bleeding. In the present study, we examined the interaction of DPAL with albumin, the most abundant plasma protein and a key transporter in the bloodstream, to assess the potential for harmful protein aggregation or structural disruption. Using dynamic light scattering and intrinsic protein fluorescence, we found that, unlike warfarin and heparin, DPAL does not induce any large protein aggregates or cause significant conformational changes near the tryptophan residue when mixed with human serum albumin, suggesting a favorable interaction profile. In addition, we used transwell permeability assays and CyQUANT cell proliferation assays to assess the cytotoxicity of DPAL in cultured human umbilical vein endothelial cells (HUVECs). Our results showed that DPAL does not compromise endothelial barrier integrity in HUVEC monolayers nor the cells’ viability. Our current and previous findings together suggest that DPAL could offer a promising approach to modulate harmful coagulation pathways and provide a new targeted therapeutic strategy for managing thrombotic disorders.
Recommended Citation
Tanujaya, Michelle; Cai, Gianna; Patel, Jia; Moldavsky, Zana; Ejaz, Yumna; Ahmed, Malia Mahazabin; Duong, SangSang; Goldfinger, Lawrence E.; Pak, Koon Y.; Gray, Brian D.; and Chong, Parkson Lee-Gau, "In Vitro Studies of the Effects of Antithrombotic Zn-Dipicolylamine-Harboring Liposomes (DPALs) on Serum Albumin and Human Umbilical Vein Endothelial Cells" (2026). Cardeza Foundation for Hematologic Research. Paper 96.
https://jdc.jefferson.edu/cardeza_foundation/96
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Language
English
Comments
This article is the author’s final published version in International Journal of Molecular Sciences, Volume 27, Issue 5, 2026, Article number 2299.
The published version is available at https://doi.org/10.3390/ijms27052299. Copyright © 2026 by the authors.