Abstract
DARPins fused with other proteins are promising non-immunoglobulin scaffolds for specific binding to target cells. In this study HER2-specific DARPin (DARPin-9-29) was used as a tumor-targeting moiety for the delivery of a cytotoxic agent - the fragment of Pseudomonas aeruginosa exotoxin A. It was determined that DARPin-PE40 possesses a considerable cytotoxic activity and induces apoptosis in HER2-positive cells. Cytotoxic effect of DARPin-PE40 strongly correlates with the HER2 expression level. The effect of intravenous administration of DARPin-PE40 was tested in the xenograft model of breast cancer. It was shown that treatment of animals with DARPin-PE40 caused strong and prolonged suppression of xenograft tumor growth.
Original language | English |
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Pages (from-to) | 48-56 |
Number of pages | 9 |
Journal | Journal of Controlled Release |
Volume | 233 |
DOIs | |
Publication status | Published - 10 Jul 2016 |
Externally published | Yes |
Keywords
- DARPin
- HER2
- PE40
- Pseudomonas aeruginosa exotoxin A
- Recombinant targeted toxin
- Targeted therapy
ASJC Scopus subject areas
- Pharmaceutical Science