Apr 14, 2020

Cabozantinib unlocks efficient in vivo targeted delivery of neutrophil-loaded nanoparticles into murine prostate tumors

BioRxiv : the Preprint Server for Biology
K. ChaudagarAkash Patnaik

Abstract

A major barrier to the successful application of nanotechnology for cancer treatment is the efficient delivery of therapeutic payloads to metastatic tumor deposits. We have previously discovered that cabozantinib, a tyrosine kinase inhibitor, triggers neutrophil-mediated anti-cancer innate immunity, resulting in tumor regression in an aggressive PTEN/p53-deficient genetically engineered murine model of advanced prostate cancer. Here, we specifically investigated the potential of cabozantinib-induced neutrophil activation and recruitment to enhance delivery of bovine serum albumin (BSA)-coated polymeric nanoparticles (NPs) into murine PTEN/p53-deficient prostate tumors. Based on the observation that BSA-coating of NPs enhanced association and internalization by activated neutrophils in vitro, relative to uncoated NPs, we systemically injected BSA-coated, dye-loaded NPs into prostate-specific PTEN/p53-deficient mice that were pre-treated with cabozantinib. Flow cytometric analysis revealed a 4-fold increase of neutrophil-associated NPs within the tumor microenvironment (TME) of mice pre-treated with cabozantinib relative to untreated controls. At steady-state, following 3 days of cabozantinib/NP administration, 1% of systemically...Continue Reading

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Mentioned in this Paper

Biological Markers
Biochemical Pathway
Transcriptional Regulation
Genes
Tumor Tissue Sample
Complex (molecular entity)
Online Mendelian Inheritance in Man (Omim) Database
PABPC1 gene
Malignant Rectal Neoplasm
Genetic Markers

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