Biomedical application of various nanoparticles (NPs) for bioimaging and therapeutic purposes attracts huge interest. In particular, NPs can be used as nanocarriers of radionuclides for radiotherapy of malignant neoplasms. However, most approaches for NP radiolabeling are complicated, and their transfer into clinical practice is difficult due to their multistep process, limited reproducibility, and lack of an automated radiolabeling procedure. Here, we develop a universal method suitable for radiolabeling of various NPs (either organic or inorganic) for internal radiotherapy of B16-F10 melanoma tumors. The obtained NPs (polylactide, silica, gold, and iron oxide) were labeled with diagnostic ( 99m Tc) and therapeutic ( 188 Re) radionuclides with a high radiolabeling efficiency (∼94− 98%) and radiochemical stability (>95%). After their intratumoral administration, these various 188 Re-labeled NPs mostly remained in the tumor, inhibiting the tumor growth rate compared to the untreated tumors. The absence of any significant leakage of the radiolabeled NPs in healthy tissues (the liver, heart, kidneys, lungs, and spleen) was confirmed by single-photon emission computed tomography (SPECT) and direct radiometry analysis. Histological analysis revealed no abnormal changes in healthy organs after the therapy (e.g., no acute pathologic findings were detected in the liver and kidneys). As a result, the treatment of mice with 188 Relabeled NPs led to a prolonged survival compared to the control group. Thus, our study provides general guidance for the use of different types of radiolabeled NPs in radionuclide therapy.
Conventional cancer therapy methods have serious drawbacks that are related to the nonspecific action of anticancer drugs that leads to high toxicity on normal cells and increases the risk of cancer recurrence. The therapeutic effect can be significantly enhanced when various treatment modalities are implemented. Here, we demonstrate that the radio-and photothermal therapy (PTT) delivered through nanocarriers (gold nanorods, Au NRs) in combination with chemotherapy in a melanoma cancer results in complete tumor inhibition compared to the single therapy. The synthesized nanocarriers can be effectively labeled with 188 Re therapeutic radionuclide with a high radiolabeling efficiency (94−98%) and radiochemical stability (>95%) that are appropriate for radionuclide therapy. Further, 188 Re−Au NRs, mediating the conversion of laser radiation into heat, were intratumorally injected and PTT was applied. Upon the irradiation of a near-infrared laser, dual photothermal and radionuclide therapy was achieved. Additionally, the combination of 188 Relabeled Au NRs with paclitaxel (PTX) has significantly improved the treatment efficiency ( 188 Re-labeled Au NRs, laser irradiation, and PTX) compared to therapy in monoregime. Thus, this local triple-combination therapy can be a step toward the clinical translation of Au NRs for use in cancer treatment.
Цель. Выявление протекторных свойств экстракта Prunella grandiflora L. (черноголовка крупноцветковая) при совместном его использовании с противораковым препаратом «Этопозид» на экспериментальной линии животных Drosophila melanogaster.Материалы и методы. В работе использовали 10%-й экстракт травы черноголовки, препарат «Этопозид» 20 мг/мл в растворе для инъекций (ОАО «Верофарм», Россия) в концентрации 800 мкг/кг питательной среды. Генотоксический эффект определяли с использованием метода SMART (Somatic Mutation And Recombination Test).Результаты. При совместном применении этопозида и 10%-го экстракта P. grandiflora показано снижение летальности у особей D. melanogaster до 15% и увеличение средней индивидуальной плодовитости в 2 раза в сравнении с использованием данного цитостатика без экстракта.Заключение. Установлено наличие антигенотоксического эффекта, который проявляется в отсутствии хромосомных аберраций, что позволяет рассмотреть возможность использования экстракта P. grandiflora в качестве компонента в диете пациентов, проходящих определенное терапевтическое лечение. Ключевые слова: лекарственные растения, антигенотоксический эффект, Drosophila melanogaster, протекторные свойства, этопозид, SMART. Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи. Источник финансирования. Работа выполнена при финансовой поддержке Правительства Российской Федерации (постановление № 211, контракт № 02.A03.21.0006).
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