Nanoformulation of PROteolysis TArgeting Chimera targeting ‘undruggable’ c-Myc for the treatment of pancreatic cancer
| Autor: | Yige Fu, Vikas V. Dukhande, Ketan Patel, Aishwarya Saraswat, Shrikant Barot, Manali Patki |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
BRD4
Biomedical Engineering Medicine (miscellaneous) Bioengineering Development 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation immune system diseases Pancreatic cancer medicine General Materials Science Viability assay Cytotoxicity health care economics and organizations 030304 developmental biology 0303 health sciences Chemistry Proteolysis targeting chimera virus diseases medicine.disease Apoptosis 030220 oncology & carcinogenesis behavior and behavior mechanisms Cancer research Cell culture assays |
| Zdroj: | Nanomedicine. 15:1761-1777 |
| ISSN: | 1748-6963 1743-5889 |
| DOI: | 10.2217/nnm-2020-0156 |
| Popis: | Aim: To explore the anticancer activity of a novel BRD4 protein degrader ARV-825 (ARV) and its nanoformulation development (ARV-NP) for treatment of pancreatic cancer. Materials & methods: ARV-NP were prepared using nanoprecipitation method and characterized for their physicochemical properties and various anticancer cell culture assays. Results: ARV-NP (89.63 ± 16.39 nm) demonstrated good physical stability, negligible hemolysis and improved half-life of ARV. ARV-NP showed significant cytotoxicity, apoptosis and anticlonogenic effect in pancreatic cancer cells. Significant downregulation of target proteins BRD4, c-Myc, Bcl-2 and upregulation of apoptotic marker cleaved caspase-3 was observed. Most importantly, ARV-NP treatment significantly inhibited the cell viability of 3D tumor spheroids of pancreatic cancer. Conclusion: ARV-NP represents a novel therapeutic strategy for pancreatic cancer. |
| Databáze: | OpenAIRE |
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