Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences , Suzhou 215123, China.
School of Materials Science and Engineering, Nanjing University of Science and Technology , Nanjing 210094, China.
Biomacromolecules. 2017 Jan 9;18(1):150-158. doi: 10.1021/acs.biomac.6b01437. Epub 2016 Dec 2.
There was much interest in the development of nanoscale delivery vehicles based on polymeric micelles to realize the diagnostic and therapeutic applications in biomedicine. Here, with the purpose of constructing a micellar magnetic resonance imaging (MRI) contrast agent (CA) with well biocompatibility and targeting specificity, two types of amphiphilic diblock polymers, mPEG-PG(DOTA(Gd))-b-PCL and FA-PEG-b-PCL, were synthesized to form mixed micelles by coassembly. The nanostructure of the resulting micellar system consisted of poly(caprolactone) (PCL) as core and poly(glycerol) (PG) and poly(ethylene glycol) (PEG) as shell, simultaneously modified with DOTA(Gd) chelates and folic acid (FA), which afforded functions of MRI contrast enhancement and tumor targeting. The mixed micelles in aqueous solution presented a hydrodynamic diameter of about 85 nm. Additionally, this mixed micelles exhibited higher r relaxivity (14.01 mM S) compared with commercial Magnevist (3.95 mM S) and showed negligible cytotoxicity estimated by WST assay. In vitro and in vivo MRI experiments revealed excellent targeting specificity to tumor cells and tissue. Furthermore, considerably enhanced signal intensity and prominent positive contrast effect were achieved at tumor region after tumor-bearing mice were intravenously injected with the mixed micelles. These preliminary results indicated the potential of the mixed micelle as T MRI CA for tumor-targeted imaging.
基于两亲性嵌段共聚物胶束的纳米递药系统在生物医药领域的诊断和治疗应用引起了广泛关注。本研究旨在构建一种具有良好生物相容性和靶向特异性的胶束磁共振成像（MRI）造影剂（CA）。为此，合成了两种两亲性嵌段共聚物 mPEG-PG(DOTA(Gd))-b-PCL 和 FA-PEG-b-PCL，用于共组装形成混合胶束。所得胶束体系的纳米结构由聚己内酯（PCL）作为核、聚甘油（PG）和聚乙二醇（PEG）作为壳组成，同时修饰有 DOTA(Gd)螯合物和叶酸（FA），赋予 MRI 对比增强和肿瘤靶向功能。在水溶液中，混合胶束的水动力学直径约为 85nm。此外，与商用 Magnevist（3.95mM S）相比，该混合胶束具有更高的 r1 弛豫率（14.01mM S），通过 WST 测定法评估显示出可以忽略不计的细胞毒性。体外和体内 MRI 实验表明，该混合胶束对肿瘤细胞和组织具有优异的靶向特异性。此外，荷瘤小鼠静脉注射混合胶束后，肿瘤部位的信号强度显著增强，呈现出明显的正对比效应。这些初步结果表明，该混合胶束作为 T1 MRI CA 用于肿瘤靶向成像具有潜在应用前景。
