Nano-synergistic combination of Erlotinib and Quinacrine for non-small cell lung cancer (NSCLC) therapeutics - Evaluation in biologically relevant in-vitro models.

作者: Bhuvaneshwar Vaidya , Vivek Gupta , Vivek Gupta , Nishant S. Kulkarni

DOI: 10.1016/J.MSEC.2021.111891

关键词: Combination therapyDrugnon-small cell lung cancer (NSCLC)Tumor progressionTherapeutic indexCancer researchMaterials scienceLung cancerErlotinibTyrosine-kinase inhibitor

摘要: Non-small cell lung cancer (NSCLC), pre-dominant subtype of cancer, is a global disorder affecting millions worldwide. One the early treatments for NSCLC was use first-generation tyrosine kinase inhibitor, Erlotinib (Erlo). However, chronic exposure to Erlo led development acquired drug resistance (ADR) in NSCLC, limiting clinical Erlo. A potential approach overcome ADR multi-drug therapy. It has been previously reported that and Quinacrine (QA), an anti-malarial drug, can work synergistically inhibit tumor progression NSCLC. combination failed at stages, citing lack efficacy. In this study, effort made improve efficacy Erlo-QA via nanoformulations, known enhance therapeutic potent chemotherapies. Synergy between QA measured estimating indices (CI). seen established nanoformulations (CI: 0.25) had better synergy than plain solutions 0.85) combination. Following extensive in-vitro testing, data were simulated biologically relevant 3D models. Two models developed 3D-Spheroids grown ultra-low attachment culture plates evaluation 5D-spheroid model 5D-sphericalplate with capability growing 750 spheroids/well protein expression analysis. Extensive studies on these revealed overall effect terms enhancement as compared Further, combinatorial therapy molecular markers evaluated 5D-Sphericalplate leading similar effects enhancement. Results from present study suggests while reducing dose.

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