MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510006, P. R. China.
College of Chemistry, Central China Normal University, Wuhan, 430079, P. R. China.
Angew Chem Int Ed Engl. 2022 Aug 15;61(33):e202204866. doi: 10.1002/anie.202204866. Epub 2022 Jul 7.
The application of G-quadruplex stabilizers presents a promising anticancer strategy. However, the molecular crowding conditions within cells diminish the potency of current G-quadruplex stabilizers. Herein, chiral Ru -Pt dinuclear complexes were developed as highly potent G-quadruplex stabilizers even under challenging molecular crowding conditions. The compounds were encapsulated with biotin-functionalized DNA cages to enhance sub-cellular localization and provide cancer selectivity. The nanoparticles were able to efficiently inhibit the endogenous activities of telomerase in cisplatin-resistant cancer cells and cause cell death by apoptosis. The nanomaterials demonstrated high antitumor activity towards cisplatin-resistant tumor cells as well as tumor-bearing mice. To the best of our knowledge, this study presents the first example of a Ru -Pt dinuclear complex as a G-quadruplex stabilizer with an anti-cancer effect towards drug-resistant tumors inside an animal model.
四链体稳定剂的应用呈现出一种很有前途的抗癌策略。然而，细胞内的分子拥挤条件降低了当前四链体稳定剂的效力。在此，手性 Ru-Pt 双核配合物被开发为即使在具有挑战性的分子拥挤条件下也具有高效的四链体稳定剂。这些化合物被封装在带有生物素功能化 DNA 笼的纳米颗粒中，以增强细胞内定位并提供癌症选择性。纳米颗粒能够有效地抑制顺铂耐药癌细胞中端粒酶的内源性活性，并通过细胞凋亡引起细胞死亡。这些纳米材料对顺铂耐药肿瘤细胞和荷瘤小鼠表现出高抗肿瘤活性。据我们所知，本研究首次报道了 Ru-Pt 双核配合物作为一种四链体稳定剂，具有针对动物模型中耐药肿瘤的抗癌作用。
