Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1761-1777 |
| Number of pages | 17 |
| Journal | Nanomedicine |
| Volume | 15 |
| Issue number | 18 |
| DOIs | |
| State | Published - Aug 2020 |
| Externally published | Yes |
Keywords
- ARV-825
- BRD4
- Drug delivery
- PROTAC
- Pancreatic ductal adenocarcinoma
- Polymeric nanoparticles