Dual-functionalized nanoparticles loaded microbubbles for enhancement of drug uptake
Dual-functionalized nanoparticles loaded microbubbles for enhancement of drug uptake
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负载微泡的双功能纳米颗粒可增强药物吸收
DOI：
10.1016/j.ultras.2018.02.003
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发表时间：
2018-07-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Ying
中科院分区：
文献类型：
--
作者：
Li, Yingjia;Zhang, Xia;Wang, Ying
微泡辅助超声的应用可以将实时成像和靶向给药的优点联合收割机结合起来。然而，MB的载药能力有限，限制了其在抗肿瘤治疗中的应用。相比之下，纳米粒（NPs）可以更有效地携带药物，但非特异性蓄积引起的不良副作用不容忽视。在此，我们开发了一种双功能化的NP负载MB，以研究其用于肿瘤靶向药物递送的潜在可行性。首先，我们制备了以肝素为骨架的纳米粒。将靶向配体叶酸和细胞穿透配体达特肽缀合至骨架以递送紫杉醇（H-F-Tat-P NP）。随后，通过抗生物素蛋白-生物素连接将双功能化的NP与MB结合，以制备负载H-F-Tat-P NP的MB（负载NP的MB）。该组合策略可以利用NP的双重功能和US引发的MB的声致孔效应。制备的NP已被表征。通过流式细胞仪和共聚焦显微镜定性和定量分析表明，细胞对纳米粒的摄取不仅与纳米粒的双重功能有关，而且与超声效应有关。最重要的是，与US组合的NPs负载的MB对叶酸受体（FR）过表达和缺陷细胞都表现出显著的细胞毒性。双功能化纳米粒和微球与超声的结合有望成为同时进行靶向抗癌药物递送和超声成像的有前途的策略。(C)2018 Elsevier B. V.版权所有。
The application of microbubble (MB)-assisted ultrasound (US) can combine the advantages of real-time imaging and targeted drug delivery. However, the drug loading capacity of MB is limited restricting its application in antitumor procedure. In contrast, nanoparticles (NPs) can carry drugs more efficiently, but adverse side effect induced by unspecific accumulation can not be ignored. Herein, we developed a dual-functionalized NP loaded MB to investigate its potential feasibility for tumor-targeted drug delivery. Firstly, we prepared NPs using heparin as backbone. Targeting ligand folate and cell-penetrating ligand Tat peptide were conjugated to the backbone to deliver paclitaxel (H-F-Tat-P NPs). Subsequently, the dual-functionalized NPs were incorporated with MBs via avidin-biotin linkage to fabricate H-F-Tat-P NPs loaded MBs (NPs-loaded MBs). The combined strategy can take profit of dual functionalities from NPs and sonoporation effect from MBs triggered by US. The prepared NPs have been characterized. The excellent cellular uptake of NPs were qualitative and quantitative analysis by flow cytometry and confocal microscope, the results indicated that it was attributed to not only dual functionalities but also US effect. Foremost, the NPs-loaded MBs combined with US exhibited significant cytotoxicity on both folate receptor (FR) overexpressing and deficiency cells. The combination of dual-functionalized NPs and MBs with US is expected to be a promising strategy for targeted anticancer drug delivery and ultrasound imaging simultaneously. (C) 2018 Elsevier B.V. All rights reserved.