Document Type

Article

Publication Date

9-25-2020

Abstract

Copyright © 2020 American Chemical Society. Colorectal cancer is one of the most significant types of cancer, ranking second in the world's mortality cases. As colorectal cancer is often diagnosed at a late stage of disease progression, effective treatments are necessary. Therefore, radiotherapy has become a fundamental approach in the treatment of colorectal cancer, especially those based on the use of 177Lu. A potential approach to meet this challenge is the use of nanotechnology through the development of radionuclide-based nanomaterials. In this work, we investigated a SiO2-derived class of nanomaterials formed by the insertion of the coordination complex, based on Eu3+ and pyrimidine-2,6-dicarboxylic acid (DPA), into nanoparticles of amino-functionalized mesoporous silica (EuDPA/SiO2-NH2). The properties of the EuDPA/SiO2-NH2 nanoparticles were initially investigated by SEM, FT-IR, TGA, and luminescence. The cellular uptake of EuDPA/SiO2-NH2 nanoparticles into HT-29 cells was confirmed by fluorescence microscopy. Radioactivity was incorporated into the EuDPA/SiO2-NH2 nanoparticles by replacing a tracer quantity of Eu3+ sites with the lanthanide element 177Lu, which resulted in the composition of a dual-modality probe for both SPECT imaging and tumor radiotherapy. Analysis of 177Lu loading into EuDPA/SiO2-NH2 particles showed efficient incorporation, up to 93% radioactivity into the final compound. The imaging potential of the 177Lu-EuDPA/SiO2-NH2 nanoparticles was investigated by SPECT/CT imaging, a subcutaneous HT-29 mouse model of colorectal cancer. Image analysis showed that tumor localization was maintained after intratumoral administration for up to 48 h. To evaluate the therapeutic potential of 177Lu-EuDPA/SiO2-NH2 nanoparticles, HT-29 xenografts were treated in vivo by direct intratumoral injection. Compared with control (PBS) treatment or treatment with unlabeled EuDPA/SiO2-NH2 nanoparticles, the treatment with 177Lu-EuDPA/SiO2-NH2 nanoparticles resulted in a significantly reduced tumor growth. Together, the results of this study results indicate that 177Lu-EuDPA/SiO2-NH2 is a promising agent for further development in SPECT imaging and clinical treatment of colorectal cancer.

Publication Source (Journal or Book title)

ACS Applied Nano Materials

First Page

8691

Last Page

8701

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