Albumin-based drug carrier targeting urokinase receptor for cancer therapy.
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| Abstract |
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.
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| Authors | Hanlin Li, Zhiyou Wang, Shujuan Yu, Shanli Chen, Yang Zhou, Yuhan Qu, Peng Xu, Longguang Jiang, Cai Yuan, Mingdong Huang |
| Journal | International journal of pharmaceutics (Int J Pharm) Vol. 634 Pg. 122636 (Mar 05 2023) ISSN: 1873-3476 [Electronic] Netherlands |
| PMID | 36696930 (Publication Type: Journal Article) |
| Copyright | Copyright © 2023. Published by Elsevier B.V. |
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