Nuclear nanomedicine using Si nanoparticles as safe and effective carriers of 188 Re radionuclide for cancer therapy

V. M. Petriev, V. K. Tischenko, A. A. Mikhailovskaya, A. A. Popov, G. Tselikov, I. Zelepukin, S. M. Deyev, A. D. Kaprin, S. Ivanov, V. Yu Timoshenko, P. N. Prasad, I. N. Zavestovskaya, A. V. Kabashin

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Abstract

Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188 Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188 Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188 Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188 Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.

Original languageEnglish
Article number2017
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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    Petriev, V. M., Tischenko, V. K., Mikhailovskaya, A. A., Popov, A. A., Tselikov, G., Zelepukin, I., Deyev, S. M., Kaprin, A. D., Ivanov, S., Timoshenko, V. Y., Prasad, P. N., Zavestovskaya, I. N., & Kabashin, A. V. (2019). Nuclear nanomedicine using Si nanoparticles as safe and effective carriers of 188 Re radionuclide for cancer therapy. Scientific Reports, 9(1), [2017]. https://doi.org/10.1038/s41598-018-38474-7