|
ИСТИНА |
Войти в систему Регистрация |
ИСТИНА ЦЭМИ РАН |
||
Effect of Surface Modification of Multifunctional Nanocomposite Drug Delivery Carriers with DARPin on Their Biodistribution $\less$i$\greater$In Vitro$\less$/i$\greater$ and $\less$i$\greater$In Vivo$\less$/i$\greater$статья
- Авторы: Novoselova Marina, Chernyshev Vasiliy S., Schulga Alexey, Konovalova Elena V., Chuprov-Netochin Roman N., Abakumova Tatiana O., German Sergei, Shipunova Victoria O., Mokrousov Maksim D., Prikhozhdenko Ekaterina, Bratashov Daniil N., Nozdriukhin Daniil V., Bogorodskiy Andrey, Grishin Oleg, Kosolobov Sergey S., Khlebtsov Boris N., Inozemtseva Olga, Zatsepin Timofei S., Deyev Sergey M., Gorin Dmitry A.
- Журнал: ACS Applied Bio Materials
- Том: 5
- Номер: 6
- Год издания: 2022
- Издательство: American Chemical Society
- Местоположение издательства: United States
- Первая страница: 2976
- Последняя страница: 2989
- DOI: 10.1021/acsabm.2c00289
- Аннотация: We present a targeted drug delivery system for therapy and diagnostics that is based on a combination of contrasting, cytotoxic, and cancer-cell-targeting properties of multifunctional carriers. The system uses multilayered polymer microcapsules loaded with magnetite and doxorubicin. Loading of magnetite nanoparticles into the polymer shell by freezing-induced loading (FIL) allowed the loading efficiency to be increased 5-fold, compared with the widely used layer-by-layer (LBL) assembly. FIL also improved the photoacoustic signal and particle mobility in a magnetic field gradient, a result unachievable by the LBL alone. For targeted delivery of the carriers to cancer cells, the carrier surface was modified with a designed ankyrin repeat protein (DARPin) directed toward the epithelial cell adhesion molecule (EpCAM). Flow cytometry measurements showed that the DARPin-coated capsules specifically interacted with the surface of EpCAM-overexpressing human cancer cells such as MCF7. In vivo and ex vivo biodistribution studies in FvB mice showed that the carrier surface modification with DARPin changed the biodistribution of the capsules toward epithelial cells. In particular, the capsules accumulated substantially in the lungs─a result that can be effectively used in targeted lung cancer therapy. The results of this work may aid in the further development of the “magic bullet” concept and may bring the quality of personalized medicine to another level.
- Добавил в систему: Зацепин Тимофей Сергеевич