Development of Theranostics Albumin Auristatin Conjugates for Combining Chemotherapy with Boron Neutron Capture Therapy | Sciact - CRIS-система Института катализа

Development of Theranostics Albumin Auristatin Conjugates for Combining Chemotherapy with Boron Neutron Capture Therapy Научная публикация

Журнал

Journal of biology and today’s world
ISSN: 2322-3308

Вых. Данные

Год: 2024, Том: 13, Номер: 1, Страницы: 000-007 Страниц : 7 DOI: 10.35248/2322-3308-13.1.001

Ключевые слова

Boronated albumin theranostic conjugates • Monomethyl auristatins • Boron neutron capture therapy • Boron delivery agents

Авторы

Wang Meiling ² , Moskalev Ivan A. ² , Zakharova Olga D. ¹ , Kasatova Anna I. ³ , Silnikov Vladimir N. ¹ , Popova Tatyana V. ^1,2 , Godovikova Tatyana S. ^1,2

Организации

1	Institute of Chemical Biology and Fundamental Medicine, SB RAS, 630090 Novosibirsk, Russia
2	Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia
3	Budker Institute of Nuclear Physics, SB RAS, 630090 Novosibirsk, Russia

Combining boron neutron capture therapy with chemotherapy can provide good therapy efficacy and is of great relevance today. In this study, we focused on serum albumin, a well-known drug delivery system, and developed homocysteine-functionalized boron albumin conjugate with chemotherapeutic molecules (monomethyl auristatin E, MMAE and auristatin F, MMAF). The new N-acylated homocysteine thiolactone bearing a cobalt bis (dicarbollide) derivative was used to create the fluorophorealbumin based construct. We report on the synthesis of a fluorophorelabeled boron-homocystamide conjugates of human serum albumin and their use in thiol-‘click’ chemistry to prepare a novel multifunctional constructs with the antitubulin agents MMAE or MMAF. We demonstrate that boron-equipped albumin conjugate with MMAE was more potent than MMAF conjugate, in the killing tumor cells. The half-maximal Inhibitory Concentration (IC50) of the designed theranostics was not less than 0.034 µM relative to T98G glioma cells with the correlation coefficient not less than R=0.88, and not less than 0.97 µM relative U 87 glioma cells with the correlation coefficient not less than R=0.71. Both theranostics are observed in vitro in the cytoplasm of human glioblastoma cells T98G as dotted small vesicles indicating an endocytic mechanism of internalization

Wang M. , Moskalev I.A. , Zakharova O.D. , Kasatova A.I. , Silnikov V.N. , Popova T.V. , Godovikova T.S.
Development of Theranostics Albumin Auristatin Conjugates for Combining Chemotherapy with Boron Neutron Capture Therapy
Journal of biology and today’s world. 2024. V.13. N1. P.000-007. DOI: 10.35248/2322-3308-13.1.001

Поступила в редакцию:	25 янв. 2024 г.
Опубликована в печати:	26 февр. 2024 г.

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