Ultrasound-Triggered Destruction of Folate-Functionalized Mesoporous Silica Nanoparticle-Loaded Microbubble for Targeted Tumor Therapy
Ultrasound-Triggered Destruction of Folate-Functionalized Mesoporous Silica Nanoparticle-Loaded Microbubble for Targeted Tumor Therapy
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DOI：
10.1002/adhm.201700354
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发表时间：
2017-09-20
影响因子：
10
通讯作者：
Zhang, Liangke
中科院分区：
文献类型：
--
作者：
Lv, Yongjiu;Cao, Yang;Zhang, Liangke
提出并制备了一种结合活性靶向介孔二氧化硅纳米粒子（MSN）和微泡（MB）药物传递系统的多功能药物传递载体。由此产生的递送载体整合了高载药量、多靶向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），以增强细胞膜转位。MSN-FA负载丹参酮IIA（TAN），然后包封在微泡中（表示为MSN-FA-TAN-MB），用于更精确的肿瘤靶向。傅立叶变换红外光谱（FTIR）证实了FA和MSN之间的结合。通过共聚焦显微镜和透射电镜研究了MSN-FA-TAN-MB的特性和形态。在A549和HeLa肿瘤细胞上进行MSN-FA-TAN-MB的体外细胞毒性和细胞摄取研究。FA-促进的MSN-FA-TAN摄取由通过FA-受体介导的内吞机制过表达FA受体的HeLa细胞显示。验证了MSN-FA-TAN-MB的超声响应特性。MSN-FA-TAN-MB在FA、MB和外部超声照射的辅助下显示出显著的体内抗肿瘤功效。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。
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.