Autor: |
Salvanou EA; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15341 Athens, Greece., Kolokithas-Ntoukas A; Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Patras, Greece., Prokopiou D; Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece., Theodosiou M; Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece., Efthimiadou E; Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece., Koźmiński P; Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 Str., 03-195 Warsaw, Poland., Xanthopoulos S; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15341 Athens, Greece., Avgoustakis K; Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Patras, Greece., Bouziotis P; Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', 15341 Athens, Greece. |
Abstrakt: |
The use of conventional methods for the treatment of cancer, such as chemotherapy or radiotherapy, and approaches such as brachytherapy in conjunction with the unique properties of nanoparticles could enable the development of novel theranostic agents. The aim of our current study was to evaluate the potential of iron oxide nanoparticles, coated with alginic acid and polyethylene glycol, functionalized with the chemotherapeutic agent doxorubicin and the monoclonal antibody bevacizumab, to serve as a nanoradiopharmaceutical agent against breast cancer. Direct radiolabeling with the therapeutic isotope Lutetium-177 ( 177 Lu) resulted in an additional therapeutic effect. Functionalization was accomplished at high percentages and radiolabeling was robust. The high cytotoxic effect of our radiolabeled and non-radiolabeled nanostructures was proven in vitro against five different breast cancer cell lines. The ex vivo biodistribution in tumor-bearing mice was investigated with three different ways of administration. The intratumoral administration of our functionalized radionanoconjugates showed high tumor accumulation and retention at the tumor site. Finally, our therapeutic efficacy study performed over a 50-day period against an aggressive triple-negative breast cancer cell line (4T1) demonstrated enhanced tumor growth retention, thus identifying the developed nanoparticles as a promising nanobrachytherapy agent against breast cancer. |