Glycofullerenes as non-receptor tyrosine kinase inhibitors- towards better nanotherapeutics for pancreatic cancer treatment

糖富勒烯作为非受体酪氨酸激酶抑制剂——朝着更好的胰腺癌治疗纳米疗法迈进

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作者:Maciej Serda, Katarzyna Malarz, Anna Mrozek-Wilczkiewicz, Marcin Wojtyniak, Robert Musioł, Steven A Curley

Abstract

The water-soluble glycofullerenes GF1 and GF2 were synthesized using two-step modified Bingel-Hirsch methodology. Interestingly, we identified buckyballs as a novel class of non-receptor Src kinases inhibitors. The evaluated compounds were found to inhibit Fyn A and BTK proteins with IC50 values in the low micromolar range, with the most active compound at 39 µM. Moreover, we have demonstrated that formation of protein corona on the surface of [60]fullerene derivatives is changing the landscape of their activity, tuning the selectivity of obtained carbon nanomaterials towards Fyn A and BTK kinases. The performed molecular biology studies revealed no cytotoxicity and no influence of engineered carbon nanomaterials on the cell cycle of PANC-1 and AsPC-1 cancer cell lines. Incubation with the tested compounds resulted in the cellular redox imbalance triggering the repair systems and influenced the changing of protein levels.

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