2025-02-11 作者：ZJ 来源：文献：Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment
文献链接：https://www.sciencedirect.com/science/article/pii/S0142961219303461
作者：Jiaqi Xua,,Yinlong Zhanga,, Junchao Xua,Meifang Wanga, Guangna Liua, Jing Wanga,Xiao Zhao, Yingqiu Qi, Jian Shi, Keman Cheng, Yao Lia, Sheng Qie,Guangjun Ni
相关产品：
原文摘要：The acquisition of stemness in colorectal cancer (CRC) attributed to the recurrence and metastasis in CRC treatment. Therefore, targeting the stemness of CRC forms a basis for the development of novel therapeutic approaches. However, the pain and systemic side effect from long-term of venipuncture injection remain great challenges to neoplastic treatment. Here, we introduce an oral drug delivery system for sustained release of BMI- 1 inhibitor (PTC209) that reverses the stemness of CRC to overcome these obstacles. In this system, nanoparticles modified with hyaluronic acid (HA) showed high-affinity to CD44/CD168 overexpressed-CRC cells, and effi-
ciently targeted to tumor site in a metastatic orthotropic colon cancer mouse model by oral administration. Significantly, the observed tumor growth inhibition is accompanied by decreased expression of stemness markers in the tumor tissues. Furthermore, HA-NPs-PTC209 also significantly prevented metastasis to the gastrointestinal system, while failing to exhibit acute side effects. In summary, we have developed an orally active, easily synthesized nanomedicine that shows promise for the treatment of colon cancer.
NH2-PEG-PLGA是一种聚合物材料。它由氨基聚乙二醇（NH2-PEG）和聚乳酸-羟基乙酸共聚物（PLGA）组成。NH2-PEG部分赋予了材料良好的水溶性和生物相容性，同时氨基的存在使其具有反应活性，可以与多种官能团进行反应。PLGA是一种可生物降解的高分子材料，具有良好的机械性能和药物缓释性能。NH2-PEG-PLGA可用于制备药物输送系统。其可通过自组装形成纳米粒子，将药物包裹在内部，实现药物的缓释和靶向输送，提高药物的Therapeutic effect 。
基于此介绍了开发了一种口服活性的，易于合成的纳米药物HA-NPs-PTC209。过程如下：
图：用NH2-PEG-PLGA和mPEG-PLGA共聚物组装ptc209负载的NPs，然后透明质酸（HA）通过EDC-NHS反应对NPs表面进行修饰。
HA-NPs-PTC209的制备
NH2-PEG-PLGA和mPEG-PLGA溶解在900 μL二氯甲烷，和PTC209（T2345-50毫克，目标分子）溶解在DMSO/甲醇被转移到一个离心管，然后水也补充。然后，用超声波发生器乳化得到初级乳液。然后加入聚乙烯醇（PVA），超声波发生器再乳化。然后将乳液缓慢滴加入 PVA中，在室温下搅拌。真空蒸发去除有机溶剂后，离心，用蒸馏水洗涤两次。
图：HA-NPs-PTC209的作用机制。
结论：NH2-PEG-PLGA和mPEG-PLGA参与制备的colon cancer-targeting纳米颗粒传递BMI-1抑制剂PTC209。通过CD44/cd168靶向配体HA的功能化，纳米颗粒在原位colon tumor中积累，以逆转CSC的干性。数据表明，纳米颗粒在体外具有相当大的稳定性，而纳米颗粒外的HA装饰使其具有良好的tumor靶向能力。这种简单的策略在体外也抑制了colon cancer细胞的克隆形成和迁移，并通过逆转干性来抑制原发tumor的体内进展和转移。
