Yang Weitao, Guo Weisheng, Gong Xiaoqun, Zhang Bingbo, Wang Sheng, Chen Na, Yang Wentao, Tu Yu, Fang Xiangming, Chang Jin
School of Materials Science and Engineering, School of Life Science, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University , Tianjin 300072, China.
CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology , No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
ACS Appl Mater Interfaces. 2015 Aug 26;7(33):18759-68. doi: 10.1021/acsami.5b05372. Epub 2015 Aug 17.
Dual-modal imaging techniques have gained intense attention for their potential role in the dawning era of tumor early accurate diagnosis. Chelate-free robust dual-modal imaging nanoprobes with high efficiency and low toxicity are of essential importance for tumor targeted dual-modal in vivo imaging. It is still a crucial issue to endow Cd-free dual-modal nanoprobes with bright fluorescence as well as high relaxivity. Herein, a facile synthetic strategy was developed to prepare Gd-doped CuInS/ZnS bimodal quantum dots (GCIS/ZnS, BQDs) with optimized properties. The fluorescent properties of the GCIS/ZnS BQDs can be thoroughly optimized by varying reaction temperature, aging time, and ZnS coating. The amount of Gd precursor can be well-controlled to realize the optimized balance between the MR relaxivity and optical properties. The obtained hydrophobic GCIS/ZnS BQDs were surface engineered into aqueous phase with PEGylated dextran-stearyl acid polymeric lipid vesicles (PEG-DS PLVs). Upon the phase transfer, the hydrophilic GCIS/ZnS@PLVs exhibited pronounced near-infrared fluorescence as well as high longitudinal relaxivity (r1 = 9.45 mM(-1) S(-1)) in water with good colloidal stability. In vivo tumor-bearing animal experiments further verified GCIS/ZnS@PLVs could achieve tumor-targeted MR/fluorescence dual-modal imaging. No toxicity was observed in the in vivo and ex vivo experiments. The GCIS/ZnS@PLVs present great potential as bimodal imaging contrast agents for tumor diagnosis.
双模态成像技术因其在肿瘤早期准确诊断的崭新时代中可能发挥的作用而备受关注。具有高效低毒特性的无螯合稳健双模态成像纳米探针对于肿瘤靶向双模态体内成像至关重要。赋予无镉双模态纳米探针明亮的荧光以及高弛豫率仍然是一个关键问题。在此，我们开发了一种简便的合成策略来制备具有优化性能的钆掺杂硫化铜铟锌双模态量子点（GCIS/ZnS，BQDs）。通过改变反应温度、老化时间和硫化锌包覆，可以全面优化GCIS/ZnS BQDs的荧光特性。可以很好地控制钆前驱体的用量，以实现磁共振弛豫率和光学性质之间的优化平衡。将得到的疏水性GCIS/ZnS BQDs用聚乙二醇化葡聚糖 - 硬脂酸聚合物脂质体（PEG-DS PLVs）进行表面工程改造，使其进入水相。在相转移后，亲水性的GCIS/ZnS@PLVs在水中表现出明显的近红外荧光以及高纵向弛豫率（r1 = 9.45 mM(-1) S(-1)），并且具有良好的胶体稳定性。体内荷瘤动物实验进一步证实GCIS/ZnS@PLVs可以实现肿瘤靶向磁共振/荧光双模态成像。在体内和体外实验中均未观察到毒性。GCIS/ZnS@PLVs作为肿瘤诊断的双模态成像造影剂具有巨大潜力。
