Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
ACS Nano. 2011 Sep 27;5(9):7462-70. doi: 10.1021/nn202399w. Epub 2011 Aug 24.
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.
靶向效率低是基于纳米颗粒药物传递系统的癌症治疗的最大限制之一。在这项研究中，开发了一种有效的肿瘤靶向药物传递方法，使用间充质干细胞作为靶向载体和二氧化硅纳米棒作为药物载体。通过细胞表面的特异性抗体-抗原识别，将载有阿霉素的二氧化硅纳米棒药物传递系统有效地锚定到间充质干细胞（MSCs）上，而无需任何细胞预处理。每个 MSC 细胞可摄取多达 1500 个纳米颗粒，且细胞活力和肿瘤趋向性高。纳米棒的细胞内保留时间不少于 48 小时，足以进行细胞导向的肿瘤趋向性传递。体内实验证明，与游离 DOX 和封装 DOX 的二氧化硅纳米棒相比，负载的 MSCs 能够更有效地追踪 U251 神经胶质瘤肿瘤细胞，并在肿瘤组织中具有更广泛的分布和更长的保留时间。增加和延长 DOX 的肿瘤内分布进一步导致肿瘤细胞凋亡明显增强。这种策略具有发展为高效、低系统毒性的靶向肿瘤治疗的强大和普遍方法的潜力。
