Nanoformulation of PROteolysis TArgeting Chimera targeting 'undruggable' c-Myc for the treatment of pancreatic cancer.

Nanomedicine
Aishwarya SaraswatKetan Patel

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.

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Citations

Mar 26, 2021·Journal of Medicinal Chemistry·Junping PeiLiang Ouyang
Jun 24, 2021·The Journal of Cell Biology·Jonathan R Whitfield, Laura Soucek

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Methods Mentioned

BETA
ubiquitination
nanoprecipitation
Dynamic light scattering
blood collection
Assay
scraping
Fluorescence
fluorescence microscopy
flow cytometry
transmission

Software Mentioned

Excel
ImageJ
Gen5 Data Analysis
GraphPad Prism7

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