Laís N Alves1,2, Sotiris Missailidis2, Claudia A S Lage3, Carlos Eduardo B DE Almeida4. 1. Laboratory of Radiobiology, Division of Medical Physics, Institute of Radioprotection and Dosimetry, Brazilian Nuclear Energy Commission, Rio de Janeiro, Brazil. 2. Institute of Technology in Immunobiologics (Bio-Manguinhos), Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. 3. Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 4. Laboratory of Radiobiology, Division of Medical Physics, Institute of Radioprotection and Dosimetry, Brazilian Nuclear Energy Commission, Rio de Janeiro, Brazil cbonacos@ird.gov.br.
Abstract
BACKGROUND: Proteins overexpressed in malignant tissues form important targets in the development of targeted therapeutics, and aptamers comprise an important affinity agent for therapy and drug delivery. In this study, aberrantly expressed mucin 1 glycoprotein was investigated as a therapeutic target in a breast cancer model. MATERIALS AND METHODS: In order to determine the feasibility of using an aptamer against mucin 1 (aptA) as carrier of the cytotoxic compound 1,10-phenanthroline to MCF-7 cells, as a potential radiosensitizer, was studied in experiments using circular dichroism and rhodamine labelling by fluorescent microscopy and flow cytometry. RESULTS: 1,10-Phenanthroline can be intercalated within aptA when complexed with Fe(II) ions, with dissociation constant (Kd) of 30 μM. The complex was subsequently capable of binding to and being internalised in MCF-7 breast cancer cells. CONCLUSION: aptA can carry 1,10-phenanthroline to cancer cells specifically and this complex represents a potential target-directed anticancer therapy. Copyright
BACKGROUND: Proteins overexpressed in malignant tissues form important targets in the development of targeted therapeutics, and aptamers comprise an important affinity agent for therapy and drug delivery. In this study, aberrantly expressed mucin 1 glycoprotein was investigated as a therapeutic target in a breast cancer model. MATERIALS AND METHODS: In order to determine the feasibility of using an aptamer against mucin 1 (aptA) as carrier of the cytotoxic compound 1,10-phenanthroline to MCF-7 cells, as a potential radiosensitizer, was studied in experiments using circular dichroism and rhodamine labelling by fluorescent microscopy and flow cytometry. RESULTS:1,10-Phenanthroline can be intercalated within aptA when complexed with Fe(II) ions, with dissociation constant (Kd) of 30 μM. The complex was subsequently capable of binding to and being internalised in MCF-7 breast cancer cells. CONCLUSION: aptA can carry 1,10-phenanthroline to cancer cells specifically and this complex represents a potential target-directed anticancer therapy. Copyright