Niu Weina, Wang Jianguo, Wang Qinyao, Shen Jianjun
Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Front Chem. 2020 Oct 30;8:574614. doi: 10.3389/fchem.2020.574614. eCollection 2020.
Ovarian cancer is a gynecological cancer from which it is difficult to be completely cured. It is common to use regimens as an effective treatment for ovarian cancer, but these inevitably bring serious side effects. New treatment strategies and special drugs are needed to improve the prognosis of patients. Celastrol is a natural product, isolated from traditional medicine, that has been proven to be curative for inflammation and cancers. However, the non-targeting and low solubility of celastrol limit its clinical application. We prepared celastrol-loaded nanoparticles for the efficient treatment of ovarian cancer via oxidative stress amplification. In this work, a tumor-targeted, ROS-sensitive nanoparticle was designed, synthesized, and assembled into a drug delivery system that used celastrol. Folic acid (FA) groups on the surface of nanoparticles guide them to actively target the surface of the tumor cell membrane. Thioketal (TK) bonds in nanoparticles can be oxidized and broken into -SH within the ROS level of tumor tissues, which causes the breaking of the PEG hydrophilic shell layer of nanoparticles and promotes the release of celastrol. The released celastrol further stimulated the production of ROS and amplified the intracellular ROS level to promote the apoptosis of tumor cells, thus achieving a therapeutic effect on the celastrol treated ovarian cancer.
卵巢癌是一种难以完全治愈的妇科癌症。使用化疗方案作为卵巢癌的有效治疗方法很常见，但这些方案不可避免地会带来严重的副作用。需要新的治疗策略和特殊药物来改善患者的预后。雷公藤红素是一种从传统药物中分离出来的天然产物，已被证明对炎症和癌症有治疗作用。然而，雷公藤红素的非靶向性和低溶解性限制了其临床应用。我们制备了负载雷公藤红素的纳米颗粒，通过氧化应激放大来有效治疗卵巢癌。在这项工作中，设计、合成并组装了一种以肿瘤为靶点、对活性氧（ROS）敏感的纳米颗粒，使其成为一种使用雷公藤红素的药物递送系统。纳米颗粒表面的叶酸（FA）基团引导它们主动靶向肿瘤细胞膜表面。纳米颗粒中的硫代酮（TK）键在肿瘤组织的ROS水平内可被氧化并断裂成 -SH，这会导致纳米颗粒的聚乙二醇（PEG）亲水壳层破裂，促进雷公藤红素的释放。释放出的雷公藤红素进一步刺激ROS的产生并放大细胞内ROS水平，以促进肿瘤细胞凋亡，从而实现对雷公藤红素治疗卵巢癌的疗效。
