PEG-PLA from PolySciTech used in development of nanoparticles for brain cancer treatment

 

PEG-PLA from PolySciTech used in development of nanoparticles for brain cancer treatment

Glioblastoma is a fast-growing and aggressive brain tumor that invades the nearby brain tissue. Treatment of it is made more difficult by the sensitivity of the area in which it is present and poor drug delivery across the blood-brain-barrier. Researchers at Harvard Medical School, Brown University, Phosphorex, Inc., Cytodigm, Inc. used PEG-PLA (AK031) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles loaded with 6-bromoindirubin-3′-acetoxime for treatment of brain cancer. This research holds promise to improve treatment of this lethal disease. Read more: Zdioruk, Mykola, Jorge-Luis Jimenez-Macias, Michal Oskar Nowicki, Katherine E. Manz, Kurt D. Pennell, Marilin S. Koch, Tomer Finkelberg et al. "PPRX-1701, a nanoparticle formulation of 6′-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models." Cell Reports Medicine (2023). https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(23)00129-5.pdf

“Highlights: PPRX-1701 is a deliverable formulation of 6-bromoindirubin-3′-acetoxime (BiA). Inhibits IDO1 expression and increases CD8 T cell infiltration in GBM mouse models. Data support investigation of this approach for future potential translation. Summary: Derivatives of the Chinese traditional medicine indirubin have shown potential for the treatment of cancer through a range of mechanisms. This study investigates the impact of 6′-bromoindirubin-3′-acetoxime (BiA) on immunosuppressive mechanisms in glioblastoma (GBM) and evaluates the efficacy of a BiA nanoparticle formulation, PPRX-1701, in immunocompetent mouse GBM models. Transcriptomic studies reveal that BiA downregulates immune-related genes, including indoleamine 2,3-dioxygenase 1 (IDO1), a critical enzyme in the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) immunosuppressive pathway in tumor cells. BiA blocks interferon-γ (IFNγ)-induced IDO1 protein expression in vitro and enhances T cell-mediated tumor cell killing in GBM stem-like cell co-culture models. PPRX-1701 reaches intracranial murine GBM and significantly improves survival in immunocompetent GBM models in vivo. Our results indicate that BiA improves survival in murine GBM models via effects on important immunotherapeutic targets in GBM and that it can be delivered efficiently via PPRX-1701, a nanoparticle injectable formulation of BiA. Keywords: glioblastoma 6-bromoindirubin-3′-acetoxime indoleamine-pyrrole 2,3-dioxygenase IDO1 tumor microenvironment”

Video: https://youtu.be/vR6bPOwY7QM

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