Zhou Fangyuan, Feng Bing, Yu Haijun, Wang Dangge, Wang Tingting, Liu Jianping, Meng Qingshuo, Wang Siling, Zhang Pengcheng, Zhang Zhiwen, Li Yaping
1. State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;; 2. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
1. State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
Theranostics. 2016 Mar 11;6(5):679-87. doi: 10.7150/thno.14556. eCollection 2016.
Theranostic nanomedicine has emerged as a promising modality for cancer diagnosis and treatment. In this study, we report the fabrication of fluorescence gold nanoclusters (GNC) conjugated with a cisplatin prodrug and folic acid (FA) (FA-GNC-Pt) for fluorescence imaging and targeted chemotherapy of breast cancer. The physio-chemical properties of FA-GNC-Pt nanoparticles are thoroughly characterized by fluorescence/UV-Vis spectroscopic measurement, particle size and zeta-potential examination. We find that FA-modification significantly accelerated the cellular uptake and increased the cytotoxicity of GNC-Pt nanoparticles in murine 4T1 breast cancer cells. Fluorescence imaging in vivo using 4T1 tumor bearing nude mouse model shows that FA-GNC-Pt nanoparticles selectively accumulate in the orthotopic 4T1 tumor and generate strong fluorescence signal due to the tumor targeting effect of FA. Moreover, we demonstrate that FA-GNC-Pt nanoparticles significantly inhibit the growth and lung metastasis of the orthotopically implanted 4T1 breast tumors. All these data imply a good potential of the GNC-based theranostic nanoplatform for fluorescence tumor imaging and cancer therapy.
诊疗纳米医学已成为一种很有前景的癌症诊断和治疗方式。在本研究中，我们报告了一种荧光金纳米簇（GNC）的制备，该纳米簇与顺铂前药和叶酸（FA）共轭（FA-GNC-Pt），用于乳腺癌的荧光成像和靶向化疗。通过荧光/紫外-可见光谱测量、粒径和zeta电位检测对FA-GNC-Pt纳米颗粒的物理化学性质进行了全面表征。我们发现FA修饰显著加速了细胞摄取，并增加了GNC-Pt纳米颗粒在小鼠4T1乳腺癌细胞中的细胞毒性。使用荷4T1肿瘤的裸鼠模型进行的体内荧光成像表明，由于FA的肿瘤靶向作用，FA-GNC-Pt纳米颗粒选择性地积聚在原位4T1肿瘤中并产生强烈的荧光信号。此外，我们证明FA-GNC-Pt纳米颗粒显著抑制原位植入的4T1乳腺肿瘤的生长和肺转移。所有这些数据表明基于GNC的诊疗纳米平台在荧光肿瘤成像和癌症治疗方面具有良好的潜力。
