Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, China.
J Nanobiotechnology. 2018 Jan 29;16(1):7. doi: 10.1186/s12951-018-0335-4.
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.
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.
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.
胰腺癌仍是癌症相关死亡的主要原因，癌症干细胞的存在和缺乏高效的早期检测可能是导致生存率低的原因。掺钆离子的上转换纳米粒子（UCNPs）为荧光与磁共振成像相结合提供了机会，它们可以提高早期胰腺癌的诊断效果。此外，作为一种在胰腺癌干细胞上过表达的跨膜糖蛋白，CD326 可以作为一种很有前途的靶点。在本研究中，我们开发了一种简便的策略，用于制备抗人 CD326 接枝的基于 UCNPs 的胶束，并对其进行了相应的表征。在进行体外和体内毒理学实验后，我们还研究了胶束在体内双模式成像中的主动靶向能力。
我们发现，通过多种表征，胶束具有优越的成像性能和长时间稳定性。通过进行体外和体内毒理学实验，胶束具有良好的生物相容性。我们观察到，在抗人 CD326 接枝到胶束的帮助下，胶束具有更好的细胞摄取能力。此外，我们成功地在人胰腺癌细胞异种移植小鼠模型中进行了双模式成像，得出 CD326 偶联胶束具有良好的主动靶向能力。
由于胶束具有良好的生物相容性和优异的成像性能，我们的结果揭示了胶束静脉注射后的高效主动归巢，这无疑证明了所获得的胶束在未来具有早期胰腺癌诊断的巨大潜力，并为后续的生物医学应用铺平了道路。
