| Autor: |
Akhmetova DR; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. akhmetova.lab.dr@gmail.com.; Laboratory of nano- and microencapsulation of biologically active compounds, Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation., Mitusova KA; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. akhmetova.lab.dr@gmail.com.; Laboratory of nano- and microencapsulation of biologically active compounds, Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation., Postovalova AS; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. akhmetova.lab.dr@gmail.com.; Granov Russian Research Center of Radiology & Surgical Technologies, Leningradskaya 70, St. Petersburg 197758, Russian Federation., Ivkina AS; Saint-Petersburg State Chemical-Pharmaceutical University, Professora Popova street 14, St. Petersburg 197376, Russian Federation., Muslimov AR; Laboratory of nano- and microencapsulation of biologically active compounds, Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation.; Scientific Center for Translational Medicine, Sirius University of Science and Technology, Olympic Ave 1, Sirius 354340, Russian Federation.; Almazov National Medical Research Centre, Akkuratova 2, St. Petersburg 197341, Russia.; RM Gorbacheva Research Institute, Pavlov University, L'va Tolstogo 6-8, St. Petersburg 197022, Russia., Zyuzin MV; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. akhmetova.lab.dr@gmail.com., Shipilovskikh SA; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. akhmetova.lab.dr@gmail.com., Timin AS; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. akhmetova.lab.dr@gmail.com.; Laboratory of nano- and microencapsulation of biologically active compounds, Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation. |
| Abstrakt: |
The size of drug carriers strongly affects their biodistribution, tissue penetration, and cellular uptake in vivo . As a result, when such carriers are loaded with therapeutic compounds, their size can influence the treatment outcomes. For internal α-radionuclide therapy, the carrier size is particularly important, because short-range α-emitters should be delivered to tumor volumes at a high dose rate without any side effects, i.e. off-target irradiation and toxicity. In this work, we aim to evaluate and compare the therapeutic efficiency of calcium carbonate (CaCO 3 ) microparticles (MPs, >2 μ m) and nanoparticles (NPs, <100 nm) labeled with radium-223 ( 223 Ra) for internal α-radionuclide therapy against 4T1 breast cancer. To do this, we comprehensively study the internalization and penetration efficiency of these MPs and NPs, using 2D and 3D cell cultures. For further therapeutic tests, we develop and modify a chelator-free method for radiolabeling of CaCO 3 MPs and NPs with 223 Ra, improving their radiolabeling efficiency (>97%) and radiochemical stability (>97%). After intratumoral injection of 223 Ra-labeled MPs and NPs, we demonstrate their different therapeutic efficiencies against a 4T1 tumor. In particular, 223 Ra-labeled NPs show a tumor inhibition of approximately 85%, which is higher compared to 60% for 223 Ra-labeled MPs. As a result, we can conclude that 223 Ra-labeled NPs have a more suitable biodistribution within 4T1 tumors compared to 223 Ra-labeled MPs. Thus, our study reveals that 223 Ra-labeled CaCO 3 NPs are highly promising for internal α -radionuclide therapy. |
