Niu Xinya, Yang He, Wu Xingkang, Huo Fangjun, Ma Kaiqing, Yin Caixia
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University Taiyuan 030006 PR China
Modern Research Center for Traditional Chinese Medicine, Shanxi University Taiyuan 030006 China.
Chem Sci. 2024 Aug 16;15(36):14924-30. doi: 10.1039/d4sc03688c.
Theranostic probes, combining diagnostic and treatment capabilities, have emerged as promising tools in tumor precision medicine. However, existing probes with constant fluorescence and photothermal activity can result in low signal-to-background ratios and phototoxicity. In this study, we introduced CM-Croc, a novel probe comprised of chromene and croconaine, selectively triggered by thiol. CM-Croc exhibited turn-on fluorescence and released croconaine for photothermal therapy. The croconaine moiety possesses high photothermal conversion efficiency up to 55%. Besides, it demonstrated potent activity against various cancer cell lines at low micromolar concentrations, including drug-resistant variants, through enhanced photothermal therapy combined with the ferroptosis effect. What's more, CM-Croc was proved to inhibit the activity of GPX4 to induce ferroptosis. Finally, CM-Croc was demonstrated to be the first croconaine-derived SOP, which targeted tumors and significantly inhibited tumor growth following intravenous administration with irradiation. This study showed CM-Croc's potential for enhancing tumor precision medicine.
诊疗探针结合了诊断和治疗能力，已成为肿瘤精准医学中有前景的工具。然而，现有的具有恒定荧光和光热活性的探针可能导致低信噪比和光毒性。在本研究中，我们引入了CM-Croc，一种由色烯和克酮酸组成的新型探针，由硫醇选择性触发。CM-Croc表现出开启荧光并释放克酮酸用于光热治疗。克酮酸部分具有高达55%的高光热转换效率。此外，通过增强光热疗法与铁死亡效应相结合，它在低微摩尔浓度下对各种癌细胞系，包括耐药变体，表现出强大的活性。更重要的是，CM-Croc被证明可抑制GPX4的活性以诱导铁死亡。最后，CM-Croc被证明是首个源自克酮酸的自噬小体，靶向肿瘤并在静脉注射并照射后显著抑制肿瘤生长。本研究表明CM-Croc在增强肿瘤精准医学方面的潜力。
