纳米药物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。肿瘤靶向效率已成为纳米药物研发和临床应用的瓶颈问题。
针对纳米材料肿瘤靶向性差这一问题，中科院理化技术研究所纳米材料可控制备与应用研究室在唐芳琼研究员的带领下，近年来一直致力于发展新型纳米载体及其生物医学应用。2009年他们发表了合成具有中空介孔结构的夹心二氧化硅的新方法（Adv. Mater. 2009, 21, 3804-3807），之后在夹心二氧化硅的生物医学应用方面做了一系列工作，相关文章发表在Angew Chem. Int. Ed.、ACS Nano、Biomaterials上。
近日，他们联合首都医科大学宣武医院、深圳市孙逸仙心血管医院、军事医学科学院、北京华美精创纳米相材料科技有限责任公司等多家单位，设计了一种全新高效的肿瘤靶向策略：将载药夹心二氧化硅纳米颗粒结合到间充质干细胞上，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，将载药纳米颗粒输送到肿瘤组织的各个部位，释放药物导致肿瘤细胞凋亡。这一全新的靶向方法采用具有趋化作用的间充质干细胞作为“靶向运输车”，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、目标性和靶向性。
该研究成果为纳米药物的肿瘤靶向方法开拓了新的思路，并为改善纳米药物临床应用带来了新的希望。审稿人认为，“他们采用了创新和有趣的纳米材料，和间充质干细胞结合，使载药纳米颗粒像子弹一样高效靶向、杀死肿瘤细胞”。
研究成果近期在《ACS纳米》（ACS Nano）上在线发表。该研究获得国家科技部“863”项目和国家自然科学基金项目的大力支持。(生物谷 Bioon.com)
doi:10.1021/nn202399w
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Silica Nanorattle–Doxorubicin-Anchored Mesenchymal Stem Cells for Tumor-Tropic Therapy
Linlin Li,Yunqian Guan,Huiyu Liu,Nanjing Hao,Tianlong Liu,Xianwei Meng,Changhui Fu,Yanzhen Li,Qiulian Qu,Yingge Zhang,Shangyi Ji,Ling Chen,Dong Chen,Fangqiong Tang,
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 was developed with mesenchymal stem cells as the targeting vehicle and a silica nanorattle as the drug carrier. A silica nanorattle–doxorubicin drug delivery system was efficiently anchored to mesenchymal stem cells (MSCs) by specific antibody–antigen recognitions at the cytomembrane interface without any cell preconditioning. Up to 1500 nanoparticles were uploaded to each MSC cell with high cell viability and tumor-tropic ability. The intracellular retention time of the silica nanorattle was no less than 48 h, which is sufficient for cell-directed tumor-tropic delivery. In vivo experiments proved that the burdened MSCs can track down the U251 glioma tumor cells more efficiently and deliver doxorubicin with wider distribution and longer retention lifetime in tumor tissues compared with free DOX and silica nanorattle-encapsulated DOX. The increased and prolonged DOX intratumoral distribution further contributed to significantly enhanced tumor-cell apoptosis. This strategy has potential to be developed as a robust and generalizable method for targeted tumor therapy with high efficiency and low systematic toxicity
