Department of Obstetrics, The First Hospital of Jilin University, Changchun, China.
Department of the Center for Reproductive Medicine, The First Hospital of Jilin University, Changchun, China.
J Biomater Appl. 2020 Aug;35(2):149-157. doi: 10.1177/0885328220924539. Epub 2020 May 9.
Nanodrug delivery systems have been widely researched to achieve efficient antitumor drug delivery. However, the controlled drug delivery at tumor cells remains the main challenge for antitumor therapy. Herein, a pH and reduction-responsive nanocarrier based on green tea polyphenols was employed as a smart excipient for chemotherapy drug delivery. Paclitaxel, as a chemotherapy drug, was loaded in the nanocarrier, noted as green tea polyphenol/paclitaxel. The green tea polyphenol/paclitaxel kept constant diameter at physiological condition (i.e. pH 7.4), while gradually enlarged at acid environment (pH = 5.5) and the reductive environment. The in vitro paclitaxel release results indicated that the release of paclitaxel from the green tea polyphenol/paclitaxel at pH 7.4 was slow, whereas obviously accelerated at the acid environment (pH = 5.5) and the reductive environment. The in vitro antitumor assay showed more efficient tumor cells inhibition of green tea polyphenol/paclitaxel than free paclitaxel. Meanwhile, due to the proper size (∼100 nm), green tea polyphenol/paclitaxel could effectively accumulate at tumor sites. In the in vivo mice bearing A549 xenograft mouse models, green tea polyphenol/paclitaxel exhibited satisfactory antitumor effect and depressed system toxicity when compared with free paclitaxel, owing to the enhanced paclitaxel accumulation and controlled paclitaxel release in the tumor cells. With simple compositions and satisfactory antitumor effects, this green tea polyphenol-based nanocarrier can be a promising nanodrug delivery system for the therapy of cancers.
纳米药物递送系统已被广泛研究，以实现高效的抗肿瘤药物递送。然而，在肿瘤细胞中实现药物的控制释放仍是抗肿瘤治疗的主要挑战。在此，我们采用基于绿茶多酚的 pH 和还原响应性纳米载体作为化疗药物递送的智能赋形剂。紫杉醇作为一种化疗药物，被装载在纳米载体中，标记为绿茶多酚/紫杉醇。在生理条件下（即 pH 7.4），绿茶多酚/紫杉醇保持恒定的直径，而在酸性环境（pH = 5.5）和还原环境中逐渐增大。体外紫杉醇释放结果表明，在 pH 7.4 时，绿茶多酚/紫杉醇中紫杉醇的释放缓慢，而在酸性环境（pH = 5.5）和还原环境中则明显加速。体外抗肿瘤试验表明，绿茶多酚/紫杉醇比游离紫杉醇更能有效抑制肿瘤细胞。同时，由于其适当的尺寸（约 100nm），绿茶多酚/紫杉醇能够有效地在肿瘤部位聚集。在荷 A549 异种移植瘤小鼠模型的体内实验中，与游离紫杉醇相比，绿茶多酚/紫杉醇表现出令人满意的抗肿瘤效果和较低的系统毒性，这归因于在肿瘤细胞中增强了紫杉醇的积累和控制了紫杉醇的释放。由于具有简单的组成和令人满意的抗肿瘤效果，这种基于绿茶多酚的纳米载体可以成为治疗癌症的一种有前途的纳米药物递送系统。
