Cytotoxicity of targeted HER2-specific phototoxins based on flavoprotein miniSOG is determined by the rate of their internalization
- Autores: Shilova O.N.1, Proshkina G.M.1, Ryabova A.V.2, Deyev S.M.1, Petrov R.V.1
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Afiliações:
- Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
- Prokhorov Institute of General Physics
- Edição: Volume 475, Nº 1 (2017)
- Páginas: 256-258
- Seção: Biochemistry, Biophysics, and Molecular Biology
- URL: https://journals.rcsi.science/1607-6729/article/view/211940
- DOI: https://doi.org/10.1134/S1607672917040044
- ID: 211940
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Resumo
The concept of targeted therapy implies the development of bifunctional agents complementing the therapeutic module with a targeting one. A promising target for the delivery of imaging and/or toxic modules is the HER2 (ErbB2) receptor. Earlier, we have functionally characterized the targeted photosensitizers 4D5scFv–miniSOG and DARPin–miniSOG, causing the death of HER2-overexpressing cells when irradiated with blue light. However, the cytotoxicity of targeted toxins 4D5scFv–miniSOG and DARPin–miniSOG (both having functionally active targeted and cytotoxic modules in recombinant proteins) against human breast adenocarcinoma cells differs 5 times. The study of the dynamics of internalization of 4D5scFv–miniSOG and DARPin–miniSOG proteins in the complex with HER2 in this work showed that the rate of internalization contributes most significantly to the toxicity of these photosensitizers, because it determines the duration of the presence of the phototoxin in the lipid bilayer of the cell membrane, where its damaging effect is maximum.
Sobre autores
O. Shilova
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
Autor responsável pela correspondência
Email: olga.shilova.n@gmail.com
Rússia, Moscow, 117997
G. Proshkina
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
Email: olga.shilova.n@gmail.com
Rússia, Moscow, 117997
A. Ryabova
Prokhorov Institute of General Physics
Email: olga.shilova.n@gmail.com
Rússia, Moscow, 119991
S. Deyev
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
Email: olga.shilova.n@gmail.com
Rússia, Moscow, 117997
R. Petrov
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
Email: olga.shilova.n@gmail.com
Rússia, Moscow, 117997
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