Application of Computational Screening Tools and Nanotechnology for Enhanced Drug Synergism in Cancer Therapy

Thu Thi Kim Ninh, Tuan Hiep Tran, Chi Ying F. Huang*, Chien Ngoc Nguyen*

*此作品的通信作者

研究成果: Article同行評審

摘要

Background: Chemoresistance continues to limit the recovery of patients with cancer. New strategies, such as combination therapy or nanotechnology, can be further improved. Objective: In this study, we applied the computational strategy by exploiting two databases (CellMiner and Prism) to sort out the cell lines sensitive to both anti-cancer drugs, paclitaxel (PTX) and dihydroar-temisinin (DHA); both of which are potentially synergistic in several cell lines. Methods: The combination of PTX and DHA was screened at different ratios to select the optimal ratio that could inhibit lung adenocarcinoma NCI-H23 the most. To further enhance therapeutic efficacy, these combinations of drugs were incorporated into a nanosystem. Results: At a PTX:DHA ratio of 1:2 (w/w), the combined drugs obtained the best combination index (0.84), indicating a synergistic effect. The drug-loaded nanoparticles sized at 135 nm with the drug loading capacity of 15.5 ± 1.34 and 13.8 ± 0.56 corresponding to DHA and PTX, respectively, were used. The nano-sized particles improved drug internalization into the cells, resulting in the significant inhibition of cell growth at all tested concentrations (p < 0.001). Additionally, α-tubulin aggregation, DNA damage suggested the molecular mechanism behind cell death upon PTX-DHA-loaded nanoparticle treatment. Moreover, the rate of apoptosis increased from approximately 5% to more than 20%, and the expression of apoptotic proteins changed 4 and 3 folds corresponding to p-53 and Bcl-2, respectively. Conclusion: This study was designed thoroughly by screening cell lines for the optimization of formu-lations. This novel approach could pave the way for the selection of combined drugs for precise cancer treatment.

原文English
頁(從 - 到)1015-1029
頁數15
期刊Current Drug Delivery
20
發行號7
DOIs
出版狀態Published - 2023

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