Journal
JOURNAL OF CONTROLLED RELEASE
Volume 344, Issue -, Pages 1-11Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2022.02.021
Keywords
Combined therapy; Therapeutic radionuclides; Calcium carbonate; Core-shell particles; Cisplatin; Lung cancer; In vivo biodistribution
Funding
- Russian Science Foundation [21-75-10044, 19-75-10010]
- Russian Federation [75-15-2021-1333 30.09.2021]
- Russian Science Foundation [19-75-10010, 21-75-10044] Funding Source: Russian Science Foundation
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This study demonstrates the potential of combined chemo-and radionuclide therapy using radionuclide carriers and chemotherapeutic drug to treat metastatic lung cancer. The developed core-shell particles effectively load therapeutic radionuclide and accumulate predominantly in lungs. Combination therapy shows superior efficacy in inhibiting tumor growth compared to single therapy.
Considering the clinical limitations of individual approaches against metastatic lung cancer, the use of combined therapy can potentially improve the therapeutic effect of treatment. However, determination of the appropriate strategy of combined treatment can be challenging. In this study, combined chemo-and radionuclide therapy has been realized using radionuclide carriers (Lu-177-labeled core-shell particles, Lu-177-MPs) and chemotherapeutic drug (cisplatin, CDDP) for treatment of lung metastatic cancer. The developed core-shell particles can be effectively loaded with Lu-177 therapeutic radionuclide and exhibit good radiochemical stability for a prolonged period of time. In vivo biodistribution experiments have demonstrated the accumulation of the developed carriers predominantly in lungs. Direct radiometry analysis did not reveal an increased absorbance of radiation by healthy organs. It has been shown that the radionuclide therapy with Lu-177-MPs in mono-regime is able to inhibit the number of metastatic nodules (untreated mice = 120 +/- 12 versus Lu-177-MPs = 50 +/- 7). The combination of chemo-and radionuclide therapy when using Lu-177-MPs and CDDP further enhanced the therapeutic efficiency of tumor treatment compared to the single therapy (Lu-177-MPs = 50 +/- 7 and CDDP = 65 +/- 10 versus Lu-177-MPs + CDDP = 37 +/- 5). Thus, this work is a systematic research on the applicability of the combination of chemo-and radionuclide therapy to treat metastatic lung cancer.
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