Albumin-based drug carrier targeting urokinase receptor for cancer therapy.

Autor: Li H; College of Chemistry, Fuzhou University, Fujian 350108, China., Wang Z; College of Chemistry, Fuzhou University, Fujian 350108, China., Yu S; College of Chemistry, Fuzhou University, Fujian 350108, China., Chen S; College of Chemistry, Fuzhou University, Fujian 350108, China., Zhou Y; College of Chemistry, Fuzhou University, Fujian 350108, China., Qu Y; College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China., Xu P; College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China., Jiang L; College of Chemistry, Fuzhou University, Fujian 350108, China., Yuan C; College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China. Electronic address: cyuan@fzu.edu.cn., Huang M; College of Chemistry, Fuzhou University, Fujian 350108, China. Electronic address: HMD_lab@fzu.edu.cn.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Mar 05; Vol. 634, pp. 122636. Date of Electronic Publication: 2023 Jan 22.
DOI: 10.1016/j.ijpharm.2023.122636
Abstrakt: Urokinase plasminogen activator receptor (uPAR) is a key participant in extracellular proteolysis, tissue remodeling and cell motility. uPAR overexpresses in most solid tumors and several hematologic malignancies, but has low levels on normal tissues, thus is advocated as a molecular target for cancer therapy. One of the obstacles for the evaluation of uPAR targeting agents in preclinical study is the species specificity, where targeting agents for human uPAR  usually not bind to murine uPAR. Here, we develop a targeting agent that binds to both murine and human uPAR. This targeting agent is genetically fused to human serum albumin, a commonly used drug carrier, and the final construct is named as uPAR targeting carrier (uPARTC). uPARTC binds specifically to uPAR-overexpressing 293T/huPAR and 293T/muPAR as demonstrated by flow cytometry. A cytotoxic compound, celastrol, is embedded into uPARTC non-covalently. The resulting macromolecular complex show effective proliferation inhibition on both murine and human uPAR overexpressing cells, and exhibit potent antitumor efficacy on hepatoma H22-bearing mice. This work demonstrates that uPARTC is a promising tumor targeting drug carrier, which address the species-specificity challenge of uPAR targeting agents and can be used to load other cytotoxic compounds.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: