TY - JOUR
T1 - 177Lu-Labeled Eu-Doped Mesoporous SiO2Nanoparticles as a Theranostic Radiopharmaceutical for Colorectal Cancer
AU - Viana, Rodrigo Da Silva
AU - Costa, Luciana Amaral De Mescana
AU - Harmon, Ashlyn C.
AU - Gomes Filho, Manoel Adrião
AU - Falcão, Eduardo H.L.
AU - Vicente, Maria G.H.
AU - Junior, Severino A.
AU - Mathis, J. Michael
N1 - Funding Information:
We gratefully acknowledge CNPq, FACEPE, and CAPES for financial support. This work was jointly supported by grants from FACEPE (grants APQ-0742-1.06/15, APQ-0675-1.06/14, and APQ-0549-1.06/17) and CNPq (grant 428020/2016-0). We acknowledge FACEPE for a Brazilian scholarship (grant IBPG-1414-3.03/14) and CAPES for an international scholarship within the Science without Borders program (88887.122971/2016-00).
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/9/25
Y1 - 2020/9/25
N2 - 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.
AB - 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.
KW - HT-29
KW - SPECT imaging
KW - colorectal cancer
KW - coordination compound
KW - dipicolinic acid
KW - lutetium-177
KW - nanoparticle photoluminescence
KW - radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=85094635116&partnerID=8YFLogxK
U2 - 10.1021/acsanm.0c01427
DO - 10.1021/acsanm.0c01427
M3 - Article
AN - SCOPUS:85094635116
SN - 2574-0970
VL - 3
SP - 8691
EP - 8701
JO - ACS Applied Nano Materials
JF - ACS Applied Nano Materials
IS - 9
ER -