Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Int J Nanomedicine. 2020 Mar 27;15:2119-2129. doi: 10.2147/IJN.S240083. eCollection 2020.
Chemotherapy is the primary treatment for advanced colon cancer, but its efficacy is often limited by severe toxicities. Targeted therapy in the form of selectively drug delivery system (SDDS) is an important strategy to reduce adverse effects. Here, we aim to design a novel SDDS with potential for practical application using biocompatible components and scalable production process, for targeted delivery of doxorubicin (Dox) to colon cancer cells.
The SDDS was made of a self-assembled DNA nano-cross (Holliday junction, or HJ) functionalized by four AS1411 aptamers (Apt-HJ) and loaded with Dox.
Apt-HJ had an average size of 12.45 nm and a zeta potential of -11.6 mV. Compared with the monovalent AS1411 aptamer, the quadrivalent Apt-HJ showed stronger binding to target cancer cells (CT26). A complex of Apt-HJ and doxorubicin (Apt-HJ-Dox) was formed by intercalating Dox into the DNA structure of Apt-HJ, with each complex carrying approximately 17 Dox molecules. Confocal microscopy revealed that Apt-HJ-Dox selectively delivered Dox into CT26 colon cancer cells but not the control cells. Moreover, Apt-HJ-Dox achieved targeted killing of CT26 cancer cells in vitro and reduced the damage to control cells. Importantly, compared with free Dox, Apt-HJ-Dox significantly enhanced the antitumor efficacy in vivo without boosting the adverse effects.
These results suggest that Apt-HJ-Dox has application potential in targeted treatment of colon cancer.
化疗是晚期结肠癌的主要治疗方法，但由于其严重的毒性作用，疗效往往受到限制。以选择性药物递送系统（SDDS）形式的靶向治疗是减少不良反应的重要策略。在这里，我们旨在使用生物相容性成分和可扩展的生产工艺设计一种新型的 SDDS，用于将阿霉素（Dox）靶向递送到结肠癌细胞。
SDDS 由四个 AS1411 适体（Apt-HJ）功能化的自组装 DNA 纳米交叉（Holliday 结，或 HJ）组成，并负载 Dox。
Apt-HJ 的平均粒径为 12.45nm，zeta 电位为-11.6mV。与单价 AS1411 适体相比，四价 Apt-HJ 与靶癌细胞（CT26）的结合能力更强。Apt-HJ 和阿霉素（Apt-HJ-Dox）复合物通过将 Dox 插入 Apt-HJ 的 DNA 结构中形成，每个复合物携带约 17 个 Dox 分子。共聚焦显微镜显示，Apt-HJ-Dox 选择性地将 Dox 递送到 CT26 结肠癌细胞中，而不是对照细胞。此外，Apt-HJ-Dox 在体外实现了对 CT26 癌细胞的靶向杀伤，同时减少了对对照细胞的损伤。重要的是，与游离 Dox 相比，Apt-HJ-Dox 在体内显著增强了抗肿瘤疗效，而没有增强不良反应。
这些结果表明，Apt-HJ-Dox 具有在结肠癌靶向治疗中的应用潜力。
