Novel Anthracycline Utorubicin for Cancer Therapy

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2021 Apr 28

PMID 33908690

Citations 8

Authors

Lorena Simon-Gracia

Valeria Sidorenko

Ain Uustare

Ivan Ogibalov

Andrus Tasa

Olga Tshubrik

Tambet Teesalu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Sidorenko V, Scodeller P, Uustare A, Ogibalov I, Tasa A, Tshubrik O Sci Rep. 2024; 14(1):17513.

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AI-assisted mass spectrometry imaging with image segmentation for subcellular metabolomics analysis.

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Targeting triple-negative breast cancer cells with a β1-integrin binding aptamer.

Pleiko K, Haugas M, Parfejevs V, Pantelejevs T, Parisini E, Teesalu T Mol Ther Nucleic Acids. 2023; 33:871-884.

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Targeting of Tomato Bushy Stunt Virus with a Genetically Fused C-End Rule Peptide.

Marchetti L, Simon-Gracia L, Lico C, Mancuso M, Baschieri S, Santi L Nanomaterials (Basel). 2023; 13(8).

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