Abstract
BackgroundPancreatic 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.ResultsWe 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.ConclusionsWith 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.
Highlights
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
As one type of transmembrane glycoprotein highly expressed in most carcinoma cells, CD326 plays a critical role in tumor progression, invasion, and metastasis, which has been considered as one biomarker of cancer stem cells [22,23,24]
Doping G d3+ into upconversion nanoparticles (UCNPs) has been demonstrated to be a facile way for realizing enhanced magnetic resonance (MR)/UCL imaging for tumors
Summary
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. Most nanoparticle approaches fall short of initial expectations when used against early stage of cancer, which is regarded as the key for potential curative therapy. This may be due to the inadequate accumulated of nanoparticles in EPR effect-lacking small clusters of disseminated tumor cells. CD326 may potentially serve as an effective tumor target for upconversion luminescence/magnetic resonance (UCL/MR) imaging simultaneously in early pancreatic cancer
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