Beijing National Laboratory for Molecular Science, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Department of Chemistry, Renmin University of China, Beijing, 100872, China.
Biomaterials. 2016 Sep;100:152-61. doi: 10.1016/j.biomaterials.2016.05.032. Epub 2016 May 24.
Great challenges remain in the noninvasive luminescence imaging analysis of tumor-targeting dynamics of nanocarriers in living animals which is of significance for the development of anti-cancer nanomedicine. In this work, luminescent nanoparticles Eu(tta)3bpt@SMA (dav = 15 nm), which exhibited good water dispersion stability and high yields of red Eu-luminescence under near-infrared two-photon excitation, were prepared by a modified microfluidic mixing method in the absence of surfactants. Tumor-targeting agents, Arg-Gly-Asp-D-Phe-Lys (cRGD) polypeptide or transferrin (Tf), were then anchored on the nanoparticle surfaces to form the desired nanocarriers Eu@SMA-RGD or Eu@SMA-Tf. The tumor-targeting processes of the prepared nanocarriers in intact living mice were analyzed on a home-built two-photon excitation time-resolved (TPE-TR) imaging apparatus having a wide view filed. The TPE-TR strategy could effectively suppress the interference from biological autofluorescence, which allowed the targeted domains to be visualized with a high signal-to-noise ratio. It was found that the tumor-tissue trapping efficacy of Eu@SMA-RGD was much higher than that of Eu@SMA-Tf, and the desorption process from the tumor tissues of Eu@SMA-RGD was slower than that of Eu@SMA-Tf. The methods developed in this work pave a way to investigate the in vivo tumor-targeting dynamics of nanocarriers by noninvasive luminescence imaging of living animals.
在活体动物中，对纳米载体的肿瘤靶向动力学进行非侵入性发光成像分析仍然存在巨大挑战，这对于抗癌纳米医学的发展具有重要意义。在这项工作中，通过改进的微流混合方法在没有表面活性剂的情况下制备了发光纳米粒子 Eu(tta)3bpt@SMA（dav = 15nm），其在近红外双光子激发下表现出良好的水分散稳定性和高的红色 Eu 发光产率。然后，肿瘤靶向剂 Arg-Gly-Asp-D-Phe-Lys（cRGD）多肽或转铁蛋白（Tf）被锚定在纳米粒子表面上，形成所需的纳米载体 Eu@SMA-RGD 或 Eu@SMA-Tf。在自制的具有宽视场的双光子激发时间分辨（TPE-TR）成像仪上分析了完整活体小鼠中制备的纳米载体的肿瘤靶向过程。TPE-TR 策略可以有效地抑制生物自发荧光的干扰，从而可以用高信噪比可视化靶向区域。结果发现，Eu@SMA-RGD 的肿瘤组织捕获效率远高于 Eu@SMA-Tf，并且 Eu@SMA-RGD 从肿瘤组织中的解吸过程比 Eu@SMA-Tf 慢。这项工作中开发的方法为通过活体动物的非侵入性发光成像研究纳米载体的体内肿瘤靶向动力学铺平了道路。
