| Autor: |
Georgij B Telegin, E. I. Shramova, N.A. Zolotova, G. M. Proshkina, D.S. Dzhalilova, M. V. Shilova, Sergey M. Deyev, Anastasiya V. Ryabova |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Journal of controlled release : official journal of the Controlled Release Society. 340 |
| ISSN: |
1873-4995 |
| Popis: |
For precise ligation of a targeting and cytotoxic moiety, the use of Barnase-Barstar pair as a molecular glue is proposed for the first time. Targeting was mediated through the use of a scaffold protein DARPin_9–29 specific for the human epidermal receptor 2 (HER2) antigen that is highly expressed on some types of cancer and Barnase*Barstar native bacterial proteins interacted with each other with Kd 10−14 M. The approach proposed consists of prelabeling a target tumor with hybrid protein DARPin-Barnase prior to administration of cytotoxic component-loaded liposomes that have Barstar covalently attached to their surface. Based on in vivo bioimaging we have proven that DARPin-based Barnase*Barstar-mediated pretargeting possesses precise tumor-targeting capability as well as antitumor activity leading to apparent tumor-growth inhibition of primary tumors and distant metastases in experimental animals. The results obtained indicate that the new system combining DARPin and Barnase*Barstar can be useful both for the drug development and for monitoring the response to treatment in vivo in preclinical studies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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Full Text from ScienceDirect