Novel Anthracycline Utorubicin for Cancer Therapy.
| Autor: | Simón-Gracia L; Institute of Biomedicine and Translational Medicine University of Tartu Ravila 14b 50411 Tartu Estonia., Sidorenko V; Institute of Biomedicine and Translational Medicine University of Tartu Ravila 14b 50411 Tartu Estonia., Uustare A; Toxinvent LLC Tiigi 61b 50410 Tartu Estonia., Ogibalov I; Toxinvent LLC Tiigi 61b 50410 Tartu Estonia., Tasa A; Toxinvent LLC Tiigi 61b 50410 Tartu Estonia., Tshubrik O; Toxinvent LLC Tiigi 61b 50410 Tartu Estonia., Teesalu T; Institute of Biomedicine and Translational Medicine University of Tartu Ravila 14b 50411 Tartu Estonia.; Cancer Research Center Sanford-Burnham-Prebys Medical Discovery Institute 10901 North Torrey Pines Road La Jolla CA 92037 USA.; Center for Nanomedicine and Department of Cell Molecular and Developmental Biology University of California Santa Barbara Santa Barbara CA 93106 USA. |
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| Jazyk: | angličtina |
| Zdroj: | Angewandte Chemie (Weinheim an der Bergstrasse, Germany) [Angew Chem Weinheim Bergstr Ger] 2021 Jul 26; Vol. 133 (31), pp. 17155-17164. Date of Electronic Publication: 2021 Jun 01. |
| DOI: | 10.1002/ange.202016421 |
| Abstrakt: | Novel anticancer compounds and their precision delivery systems are actively developed to create potent and well-tolerated anticancer therapeutics. Here, we report the synthesis of a novel anthracycline, Utorubicin (UTO), and its preclinical development as an anticancer payload for nanocarriers. Free UTO was significantly more toxic to cultured tumor cell lines than the clinically used anthracycline, doxorubicin. Nanoformulated UTO, encapsulated in polymeric nanovesicles (polymersomes, PS), reduced the viability of cultured malignant cells and this effect was potentiated by functionalization with a tumor-penetrating peptide (TPP). Systemic peptide-guided PS showed preferential accumulation in triple-negative breast tumor xenografts implanted in mice. At the same systemic UTO dose, the highest UTO accumulation in tumor tissue was seen for the TPP-targeted PS, followed by nontargeted PS, and free doxorubicin. Our study suggests potential applications for UTO in the treatment of malignant diseases and encourages further preclinical and clinical studies on UTO as a nanocarrier payload for precision cancer therapy. Competing Interests: T.T. is the inventor of patents on CendR peptides and shareholders of Cend Therapeutics Inc., a company that holds a license for the CendR peptides and is developing the peptides for clinical use. VS, LSG, OT, AT, AU, and TT are inventors of a patent application on Utorubicin (application TD 40725 / ST). (© 2021 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.) |
| Databáze: | MEDLINE |
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