177Lu-Labeled Eu-Doped Mesoporous SiO2Nanoparticles as a Theranostic Radiopharmaceutical for Colorectal Cancer

Rodrigo Da Silva Viana, Luciana Amaral De Mescana Costa, Ashlyn C. Harmon, Manoel Adrião Gomes Filho, Eduardo H.L. Falcão, Maria G.H. Vicente, Severino A. Junior, J. Michael Mathis

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)8691-8701
Number of pages11
JournalACS Applied Nano Materials
Volume3
Issue number9
DOIs
StatePublished - 25 Sep 2020

Keywords

  • colorectal cancer
  • coordination compound
  • dipicolinic acid
  • HT-29
  • lutetium-177
  • nanoparticle photoluminescence
  • radiotherapy
  • SPECT imaging

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