Khuntawee Wasinee, Amornloetwattana Rawiporn, Vongsangnak Wanwipa, Namdee Katawut, Yata Teerapong, Karttunen Mikko, Wong-Ekkabut Jirasak
Department of Physics, Faculty of Science, Kasetsart University Bangkok 10900 Thailand
Computational Biomodelling Laboratory for Agricultural Science and Technology (CBLAST), Faculty of Science, Kasetsart University Bangkok 10900 Thailand.
RSC Adv. 2021 Feb 25;11(15):8475-8484. doi: 10.1039/d1ra00038a. eCollection 2021 Feb 23.
Cordycepin or 3'-deoxyadenosine is an interesting anti-cancer drug candidate that is found in abundance in the fungus . It inhibits cellular growth of many cancers including lung carcinoma, melanoma, bladder cancer, and colon cancer by inducing apoptosis, anti-proliferation, anti-metastasis and by arresting the cell cycle. Cordycepin has, however, poor stability and low solubility in water, resulting in loss of its bioactivity. Liposomes can be used to overcome these obstacles. Our aim is to improve cordycepin's anti-colon cancer activity by liposome encapsulation. Cordycepin-encapsulated liposomes were designed and fabricated based on a combination of theoretical and experimental studies. Molecular dynamics (MD) simulations and free energy calculations suggest that phosphatidylcholine (PC) lipid environment is favorable for cordycepin adsorption. Cordycepin passively permeates into PC lipid bilayers without membrane damage and strongly binds to the lipids' polar groups by flipping its deoxyribose sugar toward the bilayer center. Our fabricated liposomes containing 10 : 1 molar ratio of egg yolk PC : cholesterol showed encapsulation efficiency (%EE) of 99% using microfluidic hydrodynamic focusing (MHF) methods. In our study using the HT-29 colon cancer cell line, cordycepin was able to inhibit growth by induction of apoptosis. Cell viability was significantly decreased below 50% at 125 μg mL dosage after 48 h treatment with non-encapsulated and encapsulated cordycepin. Importantly, encapsulation provided (1) a 2-fold improvement in the inhibition of cancer cell growth at 125 μg mL dosage and (2) 4-fold increase in release time. These and studies indicate that cordycepin-encapsulated liposomes could be a potent drug candidate for colon cancer therapy.
虫草素或3'-脱氧腺苷是一种有趣的抗癌候选药物，在真菌中大量存在。它通过诱导细胞凋亡、抗增殖、抗转移以及使细胞周期停滞来抑制多种癌症的细胞生长，包括肺癌、黑色素瘤、膀胱癌和结肠癌。然而，虫草素稳定性差且在水中溶解度低，导致其生物活性丧失。脂质体可用于克服这些障碍。我们的目标是通过脂质体包封来提高虫草素的抗结肠癌活性。基于理论和实验研究的结合，设计并制备了包封虫草素的脂质体。分子动力学（MD）模拟和自由能计算表明，磷脂酰胆碱（PC）脂质环境有利于虫草素吸附。虫草素被动渗透到PC脂质双层中而不损伤膜，并通过将其脱氧核糖糖朝向双层中心翻转而与脂质的极性基团强烈结合。我们使用微流体流体动力聚焦（MHF）方法制备的含有蛋黄PC与胆固醇摩尔比为10∶1的脂质体，其包封效率（%EE）为99%。在我们使用HT-29结肠癌细胞系的研究中，虫草素能够通过诱导凋亡来抑制生长。用未包封和包封的虫草素处理48小时后，在125μg/mL剂量下，细胞活力显著降低至50%以下。重要的是，包封提供了（1）在125μg/mL剂量下癌细胞生长抑制提高了2倍，以及（2）释放时间增加了4倍。这些研究表明，包封虫草素的脂质体可能是结肠癌治疗的一种有效候选药物。
