间充质干细胞作为多功能聚合物纳米粒子的载体用于肿瘤的靶向治疗

Low targeting efficiency is one of the biggest limitations for nanoparticulate drug delivery system-based cancer therapy. In this study, an efficient approach for tumor-targeted drug delivery would be developed with mesenchymal stem cells as the targeting vehicle and CA-PLGA-TPGS nanoparticles and/or PCLMLA nanoparticles as the drug carriers. Two nanoparticle-based drug delivery systems will be established in this research. A PCLMLA nanoparticle-based drug delivery system would be anchored to mesenchymal stem cells (MSCs) by specific antibodyantigen recognitions at the cytomembrane interface without any cell preconditioning. A CA-PLGA-TPGS nanoparticle-based drug delivery system would be internalized into the MSCs.

纳米药物载体用于恶性肿瘤治疗时最棘手的问题之一是肿瘤靶向效率较低，释放的药物难以特异性杀死肿瘤细胞。本研究中，利用新型的CA-PLGA-TPGS和PCLMLA生物可降解共聚物制备载多烯紫杉醇纳米粒，通过被间充质干细胞摄取和/或结合在间充质干细胞表面而使间充质干细胞携带载药纳米粒，由于间充质干细胞受到肿瘤细胞分泌的细胞因子的吸引，可以主动追踪到肿瘤细胞，将载药纳米粒输送到肿瘤组织，释放药物引起细胞凋亡。利用具有趋化作用的间充质干细胞作为靶向药物载体，像“特洛伊木马”一样，里应外合彻底杀死肿瘤细胞，相比传统的靶向方法具有更强的主动性和靶向性。共聚物材料中，TPGS可促进纳米粒被细胞摄取，本身具有抗肿瘤作用，还可以逆转肿瘤多药耐药。PMLA表面有多个羧基，可以连接单抗等，并且PMLA可以减轻抗癌药物对正常细胞的毒害。CA-PLGA-TPGS和PCLMLA具有辅助治疗效果，成为新一代药用辅料。

本研究设计和制备了多种新型多功能纳米颗粒，通过被间充质干细胞摄取而使其携带载药纳米粒，由于间充质干细胞受到肿瘤细胞分泌的细胞因子的吸引，可以主动追踪到肿瘤细胞，将载药纳米粒输送到肺癌组织，释放药物引起细胞凋亡。利用具有趋化作用的间充质干细胞作为靶向药物载体，像“特洛伊木马”一样，里应外合彻底杀死肿瘤细胞，相比传统的靶向方法具有更强的主动性和靶向性。本项目在Advanced Drug Delivery Reviews, Advanced Materials , Biomaterials，Theranostics, Nanoscale, ACS Applied Materials & Interfaces, Scientific Reports, Advanced Healthcare Materials, Nanomedicine:NBM, Acta Biomaterialia, Nanomedicine, Molecular Pharmaceutics和Journal of Materials Chemistry B等著名期刊发表论文32篇，其中有3篇论文入选ESI高被引论文。授权中国发明专利4项，成果荣获深圳市青年科技奖和深圳市自然科学奖二等奖。项目负责人入选教育部新世纪优秀人才、广东特支计划百千万工程青年拔尖人才，并获得广东省杰出青年科学基金资助。