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• W2790460493 abstract "Since the approval of imatinib in 2001, kinase inhibitors have revolutionized cancer therapies. Inside this family of phosphotransferases, casein kinase 2 (CK2) is of great interest and numerous scaffolds have been investigated to design CK2 inhibitors. Recently, functionalized indeno[1,2-b]indoles have been revealed to have high potency against human cancer cell lines such as MCF-7 breast carcinoma and A-427 lung carcinoma. 4-Methoxy-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (THN7), identified as a potent inhibitor of CK2 (IC50 = 71 nM), was selected for an encapsulation study in order to evaluate its antiproliferative activity as THN7-loaded cyclodextrin nanoparticles. Four α-cyclodextrins (α-CDs) were selected to encapsulate THN7 and all experiments indicated that the nanoencapsulation of this CK2 inhibitor in α-CDs was successful. No additional surface-active agent was used during the nanoformulation process. Nanoparticles formed between THN7 and α-C₆H13 amphiphilic derivative gave the best results in terms of encapsulation rate (% of associated drug = 35%), with a stability constant (K11) of 298 mol·L-1 and a size of 132 nm. Hemolytic activity of the four α-CDs was determined before the in cellulo evaluation and the α-C₆H13 derivative gave the lowest value of hemolytic potency (HC50 = 1.93 mol·L-1). Only the THN7-loaded cyclodextrin nanoparticles showing less toxicity on human erythrocytes (α-C₆H13, α-C₈H17 and α-C₄H₉) were tested against A-427 cells. All drug-loaded nanoparticles caused more cytotoxicity against A-427 cells than THN7 alone. Based on these results, the use of amphiphilic CD nanoparticles could be considered as a drug delivery system for indeno[1,2-b]indoles, allowing an optimized bioavailability and offering perspectives for the in vivo development of CK2 inhibitors." @default.
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• W2790460493 date "2018-01-26" @default.
• W2790460493 modified "2023-10-01" @default.
• W2790460493 title "Self-Assembled Supramolecular Nanoparticles Improve the Cytotoxic Efficacy of CK2 Inhibitor THN7" @default.
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• W2790460493 doi "https://doi.org/10.3390/ph11010010" @default.
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