Multimodal Imaging of Pancreatic Ductal Adenocarcinoma Using Multifunctional Nanoparticles as Contrast Agents

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作者
Zhao, Ying [1 ,2 ]
Ye, Fei [1 ,3 ]
Brismar, Torkel B. [4 ]
Li, Xuan [5 ]
He, Rui [1 ,2 ]
Heuchel, Rainer [5 ]
El-Sayed, Ramy [1 ]
Feliu, Neus [1 ,6 ]
Zheng, Wenyi [1 ,2 ]
Oerther, Sandra [1 ,2 ]
Dutta, Joydeep [3 ]
Parak, Wolfgang J. [6 ]
Muhammed, Mamoun [3 ,7 ]
Hassan, Moustapha [1 ,2 ,7 ]
机构
[1] Division of Experimental Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm,SE-141 86, Sweden
[2] Clinical Research Center, Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital-Huddinge, Stockholm,SE-141 86, Sweden
[3] KTH Royal Institute of Technology, Stockholm,SE-100 44, Sweden
[4] Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm,SE-141 86, Sweden
[5] Pancreatic Cancer Research Laboratory, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm,SE-141 86, Sweden
[6] Center for Hybrid Nanostructures (CHyN), University of Hamburg, Hamburg,22607, Germany
[7] Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria,21526, Egypt
来源
ACS Applied Materials and Interfaces | 2020年 / 12卷 / 48期
关键词
Late diagnosis and refractory behavior toward current treatment protocols make pancreatic ductal adenocarcinoma (PDAC) one of the most difficult cancer forms to treat. The imaging-based approach plays an important role to identify potentially curable PDAC patients in high-risk groups at the early stage. In the present study; we developed a core-shell structured gold nanorod (AuNR) as a contrast agent for multimodal imaging and investigated its application for PDAC diagnosis. The composite nanoparticles composed of a AuNR core inside a layer of mesoporous silica that was then coated with a gadolinium oxide carbonate shell (AuNR-SiO2-Gd) are designed to be used in magnetic resonance imaging (MRI); X-ray computed tomography (CT); and photoacoustic imaging (PAI). A phantom study with the AuNR-SiO2-Gd NPs demonstrated higher MRI contrast compared to Gadovist and higher X-ray attenuation than Visipaque. A strong; stable; and broad wavelength range signal with a peak at 800 nm was observed in PAI. The AuNR-SiO2-Gd NPs showed significant contrast enhancement under PAI/MRI/CT in both the liver and spleen of control mice after intravenous administration. The utility in PDAC was studied in a genetically engineered mouse model carrying Kras and p53 mutations; which develops spontaneous tumors and keeps the desmoplasia and hypovascularity feature of PDAC in patients. The AuNR-SiO2-Gd NPs were highly accumulated in the surrounding soft tissues but were sparsely distributed throughout the tumor due to dense stroma infiltration and poor tumor vascularization. Hence; a negative contrast within the tumor area in CT/PAI and a positive contrast in MRI were observed. In conclusion; AuNR-SiO2-Gd NPs have good potential to be developed as a multimodal contrast agent for PDAC; which might improve early diagnosis and benefit the clinical outcome for PDAC patients. ©;
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页码:53665 / 53681
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