Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Research Center for Pharmaceutical Engineering, School of Pharmacy, Chongqing Medical University, Chongqing, 400016, P. R. China.
Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing, 400016, P. R. China.
Adv Healthc Mater. 2017 Sep;6(18). doi: 10.1002/adhm.201700354. Epub 2017 Jul 3.
A multifunctional drug delivery vehicle, which combines the active targeted mesoporous silica nanoparticle (MSN) and microbubble (MB) drug delivery system, is proposed and fabricated. The resulting delivery vehicle integrates the merits of high drug loading capacity, multitargeting, and ultrasound-guided releasing. Folate (FA), which serves as an active ligand, is modified to the surface of MSN (MSN-FA) to enhance cell membrane translocation. MSN-FA is loaded with tanshinone IIA (TAN), then encapsulated in a microbubble (denoted as MSN-FA-TAN-MB) for more precise tumor targeting. The conjunction between FA and MSN is confirmed by fourier transform infrared spectroscopy (FTIR). The characteristics and morphology of MSN-FA-TAN-MB are investigated by confocal microscopy and transmission electron microscopy. In vitro cytotoxicity and cellular uptake studies of MSN-FA-TAN-MB are conducted on A549 and HeLa tumor cells. FA-facilitated MSN-FA-TAN uptake is shown by HeLa cells that overexpress FA receptors via a FA-receptor-mediated endocytosis mechanism. The ultrasound response property of MSN-FA-TAN-MB is also verified. MSN-FA-TAN-MB shows significant antitumor efficacy in vivo with the assistance of FA, MB, and an external ultrasound irradiation. Thus, this multifunctional vehicle may provide a novel strategy for tumor targeting and imaging in tumor therapy.
一种多功能药物输送载体，结合了主动靶向介孔硅纳米颗粒（MSN）和微泡（MB）药物输送系统，被提出并制备。所得的输送载体集成了高载药量、多靶向性和超声引导释放的优点。叶酸（FA）作为一种活性配体，被修饰到 MSN 的表面（MSN-FA）以增强细胞膜易位。MSN-FA 负载丹参酮 IIA（TAN），然后封装在微泡中（表示为 MSN-FA-TAN-MB）以实现更精确的肿瘤靶向。FA 与 MSN 之间的结合通过傅里叶变换红外光谱（FTIR）得到证实。通过共聚焦显微镜和透射电子显微镜研究了 MSN-FA-TAN-MB 的特性和形态。在 A549 和 HeLa 肿瘤细胞上进行了 MSN-FA-TAN-MB 的体外细胞毒性和细胞摄取研究。FA 促进了 HeLa 细胞中 MSN-FA-TAN 的摄取，这是通过 FA 受体介导的内吞作用机制，HeLa 细胞过表达了 FA 受体。还验证了 MSN-FA-TAN-MB 的超声响应特性。在 FA、MB 和外部超声辐射的辅助下，MSN-FA-TAN-MB 在体内显示出显著的抗肿瘤疗效。因此，这种多功能载体可能为肿瘤治疗中的肿瘤靶向和成像提供一种新的策略。
