Khan Arif, Alsahli Mohammed A, Aljasir Mohammad A, Maswadeh Hamzah, Mobark Mugahid A, Azam Faizul, Allemailem Khaled S, Alrumaihi Faris, Alhumaydhi Fahad A, Almatroudi Ahmad A, AlSuhaymi Naif, Khan Masood A
Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, 51452, Saudi Arabia.
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, 51452, Saudi Arabia.
J Inflamm Res. 2022 Apr 8;15:2263-2280. doi: 10.2147/JIR.S358632. eCollection 2022.
Thymoquinone (TQ), a phytoconstituent of seeds, has been studied extensively in various cancer models. However, TQ's limited water solubility restricts its therapeutic applicability. Our work aims to prepare the novel formulation of TQ and assess its chemopreventive potential in chemically induced lung cancer animal model.
The polyethylene glycol coated DOPE/CHEMS incorporating TQ-loaded pH-sensitive liposomes (TQPSL) were prepared and characterized. Mice were exposed to benzo[]pyrene (BaP) thrice a week for 4 weeks to induce lung cancer. TQPSL was administered three times a week for 21 weeks, starting 2 weeks before the first dose of BaP.
The prepared TQPSL revealed 85% entrapment efficiency with 128 nm size and -19.5 mv ζ-potential showing high stability of the formulation. The pretreatment of TQPSL showed the recovery in BaP-modulated relative organ weight of lungs, cancer marker enzymes, and antioxidant enzymes in the serum. The histopathological analysis of the tissues showed that TQPSL protected the malignancy in the lungs. The flow cytometry data revealed the induction of apoptosis and decreased intracellular ROS by TQPSL. Molecular docking was performed to predict the TQ's affinity for eight possible anticancer drug targets linked to lung cancer etiology. The data assisted to identify the serine/threonine-protein kinase BRAF as the most suitable target of TQ with binding energy -6.8 kcal/mol.
The current findings demonstrated the potential of TQPSL and its possible therapeutic targets of lung cancer. To our knowledge, this is the first research to outline the development of TQ formulation against lung cancer considering its low solubility as well as pulmonary delivery challenges.
百里醌（TQ）是种子中的一种植物成分，已在多种癌症模型中得到广泛研究。然而，TQ有限的水溶性限制了其治疗应用。我们的工作旨在制备TQ的新型制剂，并评估其在化学诱导的肺癌动物模型中的化学预防潜力。
制备并表征了负载TQ的pH敏感脂质体（TQPSL），其由聚乙二醇包被的二油酰磷脂酰乙醇胺/胆固醇组成。小鼠每周三次暴露于苯并[a]芘（BaP）中，持续4周以诱导肺癌。从首次给予BaP前2周开始，每周三次给予TQPSL，持续21周。
制备的TQPSL包封率为85%，粒径为128 nm，ζ电位为-19.5 mV，表明该制剂具有高稳定性。TQPSL预处理显示，血清中BaP调节的肺相对器官重量、癌症标志物酶和抗氧化酶有所恢复。组织的组织病理学分析表明，TQPSL可保护肺部免受恶性肿瘤侵害。流式细胞术数据显示，TQPSL可诱导细胞凋亡并降低细胞内活性氧水平。进行分子对接以预测TQ与八个与肺癌病因相关的可能抗癌药物靶点的亲和力。数据有助于确定丝氨酸/苏氨酸蛋白激酶BRAF是TQ最合适的靶点，结合能为-6.8 kcal/mol。
目前的研究结果证明了TQPSL的潜力及其可能的肺癌治疗靶点。据我们所知，这是第一项考虑到TQ低溶解度以及肺部给药挑战而概述TQ抗肺癌制剂开发的研究。
