Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, 510006, China.
J Mater Chem B. 2019 Jan 14;7(2):251-264. doi: 10.1039/c8tb02474j. Epub 2018 Dec 12.
For the treatment of malignant tumors, drug nanocarriers with long blood circulation time and ability to target the tumor microenvironment are promising therapeutic abilities. In this work, to systematically investigate the roles and functions of polysaccharides as drug nanocarriers targeting the tumor microenvironment, different types of polysaccharides (alginic acid (Alg), hyaluronic acid (HA), and dextran (Dex)) were covalently bonded with doxorubicin (DOX) through a Schiff base reaction to form a pH-sensitive polysaccharide-DOX prodrug having an acid-sensitive imine bond. After screening, Dex-DOX exhibited high drug loading content and good stability, while Alg-DOX and HA-DOX may have disadvantages such as low degree of oxidation, limited drug loading capacity, or instability in physiological conditions. Dex-DOX prodrugs were able to self-assemble into stable nanoparticles in phosphate buffered saline (PBS). Then, Dex-DOX and Dex-DOX were selected for further comparisons since they had similar drug-binding rates and long circulation time. When compared with Dex-DOX, the longer main-chain Dex-DOX showed a higher drug release rate under simulated acidic conditions in vitro, which significantly inhibited cell proliferation. Further in vivo experiments showed that Dex-DOX could more effectively improve the antitumor efficiency and survival rate while reducing side-effects. Overall, the screening and comparisons provided detailed and systematical information about the polysaccharide-DOX prodrug platform as potential antitumor drugs.
为了治疗恶性肿瘤，具有长血液循环时间和靶向肿瘤微环境能力的药物纳米载体具有有前途的治疗能力。在这项工作中，为了系统地研究多糖作为靶向肿瘤微环境的药物纳米载体的作用和功能，通过席夫碱反应将不同类型的多糖（海藻酸钠（Alg）、透明质酸（HA）和葡聚糖（Dex））共价键合到阿霉素（DOX）上，形成具有酸敏感亚胺键的 pH 敏感多糖-DOX 前药。经过筛选，Dex-DOX 表现出高载药量和良好的稳定性，而 Alg-DOX 和 HA-DOX 可能存在氧化程度低、载药量有限或生理条件下不稳定等缺点。Dex-DOX 前药能够在磷酸盐缓冲盐水（PBS）中自组装成稳定的纳米颗粒。然后，选择 Dex-DOX 和 Dex-DOX 进行进一步比较，因为它们具有相似的药物结合率和长循环时间。与 Dex-DOX 相比，具有较长主链的 Dex-DOX 在体外模拟酸性条件下表现出更高的药物释放率，显著抑制细胞增殖。进一步的体内实验表明，Dex-DOX 能够更有效地提高抗肿瘤效率和存活率，同时降低副作用。总的来说，筛选和比较为多糖-DOX 前药平台作为潜在抗肿瘤药物提供了详细和系统的信息。
