Self-assembled ruthenium and osmium nanosystems display a potent anticancer profile by interfering with metabolic activity.
Self-assembled ruthenium and osmium nanosystems display a potent anticancer profile by interfering with metabolic activity.
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DOI：
10.1039/d2qi00423b
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发表时间：
2022-06-07
影响因子：
7
通讯作者：
Berger, Gilles
中科院分区：
文献类型：
--
作者：
Marloye, Mickael;Inam, Haider;Moore, Connor J.;Mertens, Tyler R.;Ingels, Aude;Koch, Marilin;Nowicki, Michal O.;Mathieu, Veronique;Pritchard, Justin R.;Awuah, Samuel G.;Lawler, Sean E.;Meyer, Franck;Dufrasne, Francois;Berger, Gilles
我们公开了新型两亲性钌和锇络合物，它们通过抑制线粒体呼吸自动组装成具有有效抗增殖活性的纳米药物。自组装单元是从[M(对伞花烃)(1,10-菲咯啉)Cl]PF6基序（其中M是RuII或OsII）合理设计的，附加C16脂肪链，以实现高细胞活性、纳米组装和线粒体靶向。这些两亲性复合物可在亚微摩尔范围内阻止细胞增殖，并且对由患者来源的癌症干细胞制成的胶质母细胞瘤神经球特别有效。使用这些胶质母细胞瘤干细胞的皮下小鼠模型凸显了我们的一种 C16 OsII 纳米药物在体内非常成功。从机制上讲，我们表明它们充当代谢毒物，强烈损害线粒体呼吸，形态变化和线粒体损伤证实了这一点。基于 RNAi 的遗传策略进一步了解了微管作为诱导细胞死亡的一部分的潜在参与作用。与此同时，我们研究了这些新型两亲金属基结构的结构特性、它们的反应性和机制。
We disclose novel amphiphilic ruthenium and osmium complexes that auto-assemble into nanomedicines with potent antiproliferative activity by inhibition of mitochondrial respiration. The self-assembling units were rationally designed from the [M(p-cymene)(1,10-phenanthroline)Cl]PF6 motif (where M is either RuII or OsII) with an appended C16 fatty chain to achieve high cellular activity, nano-assembling and mitochondrial targeting. These amphiphilic complexes block cell proliferation at the sub-micromolar range and are particularly potent towards glioblastoma neurospheres made from patient-derived cancer stem cells. A subcutaneous mouse model using these glioblastoma stem cells highlights one of our C16 OsII nanomedicines as highly successful in vivo. Mechanistically, we show that they act as metabolic poisons, strongly impairing mitochondrial respiration, corroborated by morphological changes and damage to the mitochondria. A genetic strategy based on RNAi gave further insight on the potential involvement of microtubules as part of the induced cell death. In parallel, we examined the structural properties of these new amphiphilic metal-based constructs, their reactivity and mechanism.
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影响因子：
3
作者：
Betanzos-Lara, Soledad;Novakova, Olga;Habtemariam, Abraha
通讯作者：
Habtemariam, Abraha
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A
影响因子：
4.9
作者：
Delaude, L;Delfosse, S;Noels, AF
通讯作者：
Noels, AF
影响因子：
8.8
作者：
Aird, R E;Cummings, J;Ritchie, A A;Muir, M;Morris, R E;Chen, H;Sadler, P J;Jodrell, D I
通讯作者：
Jodrell, D I
影响因子：
5.6
作者：
Ghuman, J;Zunszain, PA;Curry, S
通讯作者：
Curry, S