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Facile assembly of upconversion nanoparticle-based micelles for active targeted dual-mode imaging in pancreatic cancer

机译:基于上转化的纳米粒子胶束的容易组装用于胰腺癌中的活性靶向双模成像

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Abstract Background Pancreatic cancer remains the leading cause of cancer-related deaths, the existence of cancer stem cells and lack of highly efficient early detection may account for the poor survival rate. Gadolinium ion-doped upconversion nanoparticles (UCNPs) provide opportunities for combining fluorescent with magnetic resonance imaging, and they can improve the diagnostic efficacy of early pancreatic cancer. In addition, as one transmembrane glycoprotein overexpressed on the pancreatic cancer stem cells, CD326 may act as a promising target. In this study, we developed a facile strategy for developing anti-human CD326-grafted UCNPs-based micelles and performed the corresponding characterizations. After conducting in vitro and vivo toxicology experiments, we also examined the active targeting capability of the micelles upon dual-mode imaging in vivo. Results We found that the micelles owned superior imaging properties and long-time stability based on multiple characterizations. By performing in vitro and vivo toxicology assay, the micelles had good biocompatibility. We observed more cellular uptake of the micelles with the help of anti-human CD326 grafted onto the micelles. Furthermore, we successfully concluded that CD326-conjugated micelles endowed promising active targeting ability by conducting dual-mode imaging in human pancreatic cancer xenograft mouse model. Conclusions With good biocompatibility and excellent imaging properties of the micelles, our results uncover efficient active homing of those micelles after intravenous injection, and undoubtedly demonstrate the as-obtained micelles holds great potential for early pancreatic cancer diagnosis in the future and would pave the way for the following biomedical applications.
机译:摘要背景胰腺癌仍然是癌症相关死亡的主要原因,癌症干细胞的存在性和缺乏高效的早期检测可能会占存活率差的差。钆离子掺杂的上转换纳米颗粒(UCNP)为将荧光与磁共振成像组合的机会提供了组合,它们可以提高早期胰腺癌的诊断疗效。另外,作为在胰腺癌干细胞上过表达的一种跨膜糖蛋白,CD326可以作为有前途的靶标。在这项研究中,我们开发了一种用于开发抗人CD326接枝的基于UCNP的胶束并进行相应的表征。在体外和体内毒理学实验中进行后,我们还在体内双模成像时检查了胶束的主动靶向能力。结果我们发现胶束基于多种特征拥有卓越的成像性能和长时间稳定性。通过在体外和体内毒理学测定中进行,胶束具有良好的生物相容性。在接枝到胶束上的抗人CD326的帮助下,我们观察到更多细胞摄取胶束。此外,我们通过在人胰腺癌异种移植小鼠模型中进行双模成像,成功地结论了CD326-缀合的胶束赋予有前途的活性靶向能力。结论胶束的良好生物相容性和优异的成像性能,我们的结果在静脉注射后发现了胶束的有效活跃的摩托,无疑证明了未来的胶束对早期胰腺癌诊断的巨大潜力并将铺平以下生物医学应用程序。

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