Cube-shaped theranostic paclitaxel prodrug nanocrystals with surface functionalization of SPC and MPEG-DSPE for imaging and chemotherapy
Cube-shaped theranostic paclitaxel prodrug nanocrystals with surface functionalization of SPC and MPEG-DSPE for imaging and chemotherapy
复制标题
用于成像和化疗的具有 SPC 和 MPEG-DSPE 表面功能化的立方形治疗诊断紫杉醇前药纳米晶体
DOI：
10.1016/j.colsurfb.2017.10.013
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发表时间：
2017-12-01
影响因子：
5.8
通讯作者：
Su, Guanghao
中科院分区：
文献类型：
--
作者：
Guo, Fuqiang;Shang, Jiajia;Su, Guanghao
药物纳米晶体作为纳米药物递送系统之一，具有良好的抗癌作用。近年来，纳米晶体药物和小分子游离药物在内化机制和亚细胞定位方面的差异引起了人们的广泛关注。本文采用4-氯-7-硝基- 1,2,3 -苯并恶二唑（NBD-Cl） (Ma et al. (2016) and Wang et al. （2016) [1,2] (PTX- nbd)）直接标记紫杉醇（PTX）作为模型抗癌药物。通过PTX与NBD-Cl的亲核取代反应，高收率合成了PTX- nbd，并通过荧光、XRD、ESI-MS和FT-IR分析对其进行了表征。随后，采用反溶剂法制备了立方型PTX-NBD纳米晶体，并对SPC和MPEG-DSPE进行了表面功能化。所制得的形状特异的PTX-NBD@PC-PEG纳米颗粒流体力学粒径约为50 nm，胶体稳定性好，载药量高达64%。此外，与游离PTX-NBD和表面功能化SPC和MPEG-DSPE的球形PTX-NBD纳米晶体（PTX-NBD@PC-PEG NSs）相比，PTX-NBD@PC-PEG NCs显著减少了爆发释放，提高了细胞摄取效率和体外癌细胞杀伤能力。总之，这项工作强调了基于药物-荧光基团偶联物的治疗前药物纳米晶体在细胞成像和化疗方面的潜力。(C) 2017 Elsevier B.V.版权所有
As one of nanomedicine delivery systems (NDSs), drug nanocrystals exhibited an excellent anticancer effect. Recently, differences of internalization mechanisms and subcellular localization of both drug nanocrystals and small molecular free drug have drawn much attention. In this paper, paclitaxel (PTX) as a model anticancer drug was directly labeled with 4-chloro-7-nitro-1, 2, 3-benzoxadiazole (NBD-Cl) (a drug-fluorophore conjugate Ma et al. (2016) and Wang et al. (2016) [1,2] (PTX-NBD)). PTX-NBD was synthesized by nucleophilic substitution reaction of PTX with NBD-Cl in high yield and characterized by fluorescence, XRD, ESI-MS, and FT-IR analysis. Subsequently, the cube-shaped PTX-NBD nanocrystals were prepared with an antisolvent method followed by surface functionalization of SPC and MPEG-DSPE. The obtained specific shaped PTX-NBD@PC-PEG NCs had a hydrodynamic particle size of similar to 50 nm, excellent colloidal stability, and a high drug-loading content of similar to 64%. Moreover, in comparison with free PTX-NBD and the sphere-shaped PTX-NBD nanocrystals with surface functionalization of SPC and MPEG-DSPE (PTX-NBD@PC-PEG NSs), PTX-NBD@PC-PEG NCs remarkably reduced burst release and improved cellular uptake efficiency and in vitro cancer cell killing ability. In a word, the work highlights the potential of theranostic prodrug nanocrystals based on the drug-fluorophore conjugates for cell imaging and chemotherapy. (C) 2017 Elsevier B.V. All rights reserved.