新型可降解多孔硅材料用于肺癌靶向药物输运系统的研究

Targeted transport and release is the main development direction of nano-drug carrier. This project proposes a new drug delivery system which can hierarchical targeting lung tumor: preparation of a new type of antitumor drug transport which has a ability of size dependent targeting lung, with the degradability of porous silicon. In this drug system, an enzyme sensitive nanodrugs which can active target lung cancer cells will be loaded into the pores of silicon particles. The anticancer drugs will realize in a hierarchical sustained-release behavior. The delivery system can effectively escape biological barriers, and aggregate in fixed-point in vivo. It will improve the targeting property of nanodrugs. The design of nanodrugs depends on the tumor microenvironment. For the lower toxicity of paclitaxel, the cathepsin B sensitive GFLG peptide is used to connect the anti-cancer drug paclitaxel and polymer (PEG - PLGA). And then a RGD signal peptide will be modified on the surface of nanodrugs microspheres, which can be targeted to cancer cell. It will promote the targeted ability. Finally the nanodrugs are loaded into the porous silicon particles delivery vehicles. This porous silicon transport vehicles can effectively protect nanodrugs escape biological barriers, transfer the cargos to the fixed-point in lung tissue. It will promote nanodrugs in the targeted lung tissue to kill tumor cells. This study can effectively improve the anti-tumor drug targeting transport performance and controlled release behavior. It will have a good potential application prospect in the field of tumor treatment.

靶向输运和控制释放是纳米药物输运系统发展的重要方向。本项目提出一种新型可降解的多孔硅材料用于肺癌的靶向治疗：制备一种新型的具有尺寸依赖肺靶向的可降解多孔硅颗粒作为新型抗肿瘤药物的输运器，装载具有主动靶向肿瘤细胞的纳米药物，实现抗肿瘤药物的分级缓释。该输运系统可以有效逃逸生物屏障，增加药物的肺部累积，提高药物的靶向性。纳米药物依赖于肿瘤微环境变化，以组织蛋白酶B敏感的GFLG肽链连接抗癌药物紫杉醇和聚合物高分子PEG-PLGA，构建酶敏感型纳米药物，并结合主动靶向分子修饰到纳米微球表面，提高纳米药物的主动靶向。最后将纳米药物装载进多孔硅输运器，实现新型药物载体的全制备。多孔硅输运器能有效保护纳米药物逃逸生物屏障，实现肺部组织的定点累积和释放；促进纳米药物在肺部组织的分级靶向杀死肿瘤细胞。该研究能够有效提高目前抗肿瘤药物的靶向输运和控制释放，在肿瘤治疗领域有着良好的应用前景。

靶向输运和控制释放是纳米药物输运系统发展的重要方向。本项目提出一种新型可降解的多孔硅材料用于肺癌的靶向治疗：制备一种新型的具有尺寸依赖肺靶向的可降解多孔硅颗粒作为新型抗肿瘤药物的输运器，装载具有主动靶向肿瘤细胞的纳米药物，实现抗肿瘤药物的分级缓释。该输运系统可以有效逃逸生物屏障，增加药物的肺部累积，提高药物的靶向性。纳米药物依赖于肿瘤微环境变化，以组织蛋白酶B敏感的GFLG肽链连接抗癌药物紫杉醇和聚合物高分子PEG-PLGA，构建酶敏感型纳米药物，并结合主动靶向分子修饰到纳米微球表面，提高纳米药物的主动靶向。最后将纳米药物装载进多孔硅输运器，实现新型药物载体的全制备。多孔硅输运器能有效保护纳米药物逃逸生物屏障，实现肺部组织的定点累积和释放；促进纳米药物在肺部组织的分级靶向杀死肿瘤细胞。该研究能够有效提高目前抗肿瘤药物的靶向输运和控制释放，在肿瘤治疗领域有着良好的应用前景。