RAS PresidiumДоклады Российской академии наук. Науки о жизни Doklady Biological Sciences

  • ISSN (Print) 2686-7389
  • ISSN (Online) 3034-5057

GALA3-containing modular nanotransporters are capable of delivering Keap1 monobody to target cells and inhibiting the formation of reactive oxygen species in the cells

PII
S2686738925010268-1
DOI
10.31857/S2686738925010268
Publication type
Article
Status
Published
Authors
Volume/ Edition
Volume 520 / Issue number 1
Pages
159-163
Abstract
In the previously created modular nanotransporter (MNT) capable of delivering a monobody to Keap1 into the cytosol, the translocation domain of diphtheria toxin (DTox) was replaced by the endosomolytic peptide GALA3. It was found that this substitution more than doubles the lifetime of MNT in the blood. Using confocal microscopy, it was shown that MNT with GALA3 was internalized into AML12 cells mainly due to binding to the epidermal growth factor receptor, and is also able to exit from endosomes into the cytosol. Using cellular thermal shift assay, it was shown that MNT with GALA3 and MNT with DTox are equally effective in disrupting the formation of the Nrf2 complex with Keap1, which led to similar protection of AML12 cells from the action of hydrogen peroxide. The obtained results allow not only to optimize the systemic use of MNT, but can also serve as a basis for creating agents aimed at treating diseases associated with oxidative stress.
Keywords
модульные нанотранспортеры GALA3 транслокационный домен дифтерийного токсина время жизни в крови конфокальная микроскопия проточная цитофлуориметрия клеточный анализ теплового сдвига
Date of publication
15.09.2025
Year of publication
2025
Number of purchasers
0
Views
19

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