School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Mol Pharm. 2022 Jan 3;19(1):35-50. doi: 10.1021/acs.molpharmaceut.1c00565. Epub 2021 Dec 10.
Mitochondria are involved in the regulation of apoptosis, making them a promising target for the development of new anticancer drugs. Doxorubicin (DOX), a chemotherapeutic drug, can induce reactive oxygen species (ROS)-mediated apoptosis, improving its anticancer effects. Herein, Rhein, an active ingredient in rhubarb, with the capability of self-assembly and mitochondrial targeting, was used in conjunction with DOX to form efficient nanomaterials (Rhein-DOX nanogel) capable of sustained drug release. It was self-assembled with a hydrogen bond, π-π stacking interactions, and hydrophobic interactions as the main driving force, and its loading efficiency was up to 100%. Based on its self-assembly characteristics, we evaluated the mechanism of this material to target mitochondria, induce ROS production, and promote apoptosis. The IC of the Rhein-DOX nanogel (3.74 μM) was only 46.3% of that of DOX (11.89 μM), and the tumor inhibition rate of the Rhein-DOX nanogel was 79.4% in vivo, 2.3 times that of DOX. This study not only addresses the disadvantages of high toxicity of DOX and low bioavailability of Rhein, when DOX and Rhein are combined for the treatment of hepatoma, but it also significantly improved the synergistic antihepatoma efficacy of Rhein and DOX, which provides a new idea for the development of long-term antihepatoma agents with low toxicity.
线粒体参与细胞凋亡的调控，使其成为开发新型抗癌药物的有前途的靶点。多柔比星（DOX）是一种化疗药物，可诱导活性氧（ROS）介导的细胞凋亡，从而提高其抗癌效果。在此，大黄中的一种活性成分大黄酸（Rhein）具有自组装和靶向线粒体的能力，与 DOX 结合形成能够持续释放药物的高效纳米材料（Rhein-DOX 纳米凝胶）。它主要通过氢键、π-π堆积相互作用和疏水相互作用自组装，载药效率高达 100%。基于其自组装特性，我们评估了该材料靶向线粒体、诱导 ROS 产生和促进细胞凋亡的机制。Rhein-DOX 纳米凝胶的 IC（3.74 μM）仅为 DOX（11.89 μM）的 46.3%，Rhein-DOX 纳米凝胶在体内的肿瘤抑制率为 79.4%，是 DOX 的 2.3 倍。这项研究不仅解决了 DOX 毒性高和 Rhein 生物利用度低的缺点，而且当 DOX 和 Rhein 联合用于肝癌治疗时，还显著提高了 Rhein 和 DOX 的协同抗肝癌疗效，为开发低毒性的长期抗肝癌药物提供了新的思路。
