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首页> 外文期刊>Materials science & engineering >Nano-synergistic combination of Erlotinib and Quinacrine for non-small cell lung cancer (NSCLC) therapeutics - Evaluation in biologically relevant in-vitro models
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Nano-synergistic combination of Erlotinib and Quinacrine for non-small cell lung cancer (NSCLC) therapeutics - Evaluation in biologically relevant in-vitro models

机译：非小细胞肺癌（NSCLC）治疗剂的南非协同组合和非小细胞肺癌（NSCLC）治疗 - 在体外模型中生物相关性的评价

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Non-small cell lung cancer (NSCLC), pre-dominant subtype of lung cancer, is a global disorder affecting millions worldwide. One of the early treatments for NSCLC was use of a first-generation tyrosine kinase inhibitor, Erlotinib (Erlo). However, chronic exposure to Erlo led to development of acquired drug resistance (ADR) in NSCLC, limiting the clinical use of Erlo. A potential approach to overcome development of ADR is a multi-drug therapy. It has been previously reported that Erlo and Quinacrine (QA), an anti-malarial drug, can work synergistically to inhibit tumor progression in NSCLC. However, the combination failed at clinical stages, citing lack of efficacy. In this study, an effort has been made to improve the efficacy of Erlo-QA combination via development of nanoformulations, known to enhance therapeutic efficacy of potent chemotherapies. Synergy between Erlo and QA was measured via estimating the combination indices (CI). It was seen that established combination of nanoformulations (CI: 0.25) had better synergy than plain drug solutions (CI: 0.85) in combination. Following extensive in-vitro testing, data were simulated in biologically relevant 3D tumor models. Two tumor models were developed for extensive in-vitro testing, 3D-Spheroids grown in ultra-low attachment culture plates for efficacy evaluation and a 5D-spheroid model in 5D-sphericalplate with capability of growing 750 spheroids/well for protein expression analysis. Extensive studies on these models revealed that combination of Erlo and QA nanoformulations overall had a better effect in terms of synergy enhancement as compared to plain drug combination. Further, effect of combinatorial therapy on molecular markers was evaluated on 5D-Sphericalplate leading to similar effects on synergy enhancement. Results from present study suggests that combination of nanoformulations can improve the synergy between Erlo and QA while reducing the overall therapeutic dose.
机译：非小细胞肺癌（NSCLC），肺癌的占优势亚型，是一种影响全球数百万的全球性疾病。 NSCLC的早期处理之一是使用第一代酪氨酸激酶抑制剂，Erlotinib（ERLO）。然而，慢性暴露于ERLO导致NSCLC中获得的耐药性（ADR）的发展，限制了ERLO的临床应用。克服ADR发育的潜在方法是多药物治疗。先前已经报道，ERLO和喹吖啶（QA）是一种抗疟疾药物，可以协同作用地抑制NSCLC中的肿瘤进展。然而，组合在临床阶段失败，引起了缺乏功效。在这项研究中，已经努力提高Erlo-QA组合通过纳米族种植的效果，已知有利于增强有效化疗的治疗效果。通过估计组合指数（CI）测量ERLO和QA之间的协同作用。可以看出，建立纳米族种族（CI：0.25）的组合优于普通药物溶液（CI：0.85）。在广泛的体外测试之后，在生物相关的3D肿瘤模型中模拟数据。在超低附着培养板中生长的3D球形，用于功效评价的3D-球形，在5D球板中产生了两种肿瘤模型，用于5D-球板中的5D-球形模型，具有蛋白质表达分析的750球形/孔的能力。关于这些模型的广泛研究表明，与普通药物组合相比，ERLO和QA纳米型和QA纳米族种族的组合在协同增强方面具有更好的效果。此外，对5D-球板的组合治疗对分子标记物的影响，导致对协同增强的影响相似。目前研究的结果表明，纳米族种类的组合可以改善Erlo和QA之间的协同作用，同时减少整体治疗剂量。

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