Novel Anthracycline Utorubicin for Cancer Therapy

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. Utorubicin (UTO) is a novel anthracycline with higher anticancer activity than doxorubicin in cultured cancer cells. Nanoencapsulation of UTO in polymeric vesicles functionalized with tumor‐penetrating peptides increases the cytotoxicity of the drug in receptor‐positive cells in vitro and, after systemic administration into mice bearing triple‐negative tumors, potentiates UTO accumulation in malignant tissue.