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Size-dependent therapeutic efficiency of 223 Ra-labeled calcium carbonate carriers for internal radionuclide therapy of breast cancer.
Biomaterials Science 2023 December 8
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 (CaCO3 ) 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 CaCO3 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 CaCO3 NPs are highly promising for internal α -radionuclide therapy.
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