Description:
Project ID: D2021-13
Background:
Patients affected by pancreatic ductal adenocarcinoma (PDAC), an aggressive type of cancer, have a 5-year survival rate of 9%, the lowest of any cancer in the US. Therapies for pancreatic cancer are largely hindered by the lack of an effective delivery system. Exosomes are emerging as promising nanocarriers for genes and drugs; however, major challenges exist including the absence of active tumor targeting and a high proportion of clearance by mononuclear phagocytic system (MPS) in liver and spleen. There remains a need in the art for new and improved compositions and methods for treating pancreatic cancer.
Invention Summary:
Researchers at the University of Toledo have developed a unique and innovative exosome-based delivery system in which engineered exosomes can simultaneously target PDAC tumor cells and reduce phagocyte immune system clearance. The novel smart exosome was generated by engineering the CD9, an exosome marker, to display a HA tagged RGD peptide at the E174 site of CD9 (CD9-HA-RGD). The exosomes are advantageous for delivering therapeutic agents to treat diseases with targeted precision, and for evading clearance by macrophages. Exosomes achieved enhanced cell binding and increased uptake capacities in an avb3 expression dependent manner in PDAC cells. Exosomes resulted in 71.5% reduction of macrophage phagocytosis when compared to control exosomes as evaluated by THP1 cells phagocytosis assay. The newly designed exosome may have a better translational potential in PDAC diagnosis and therapy than traditional exosomes.
Application:
Treatment of pancreatic cancer (Drug Delivery)
Advantages:
- Smart exosomes can achieve highly effective PDAC targeting simultaneously with minimal MPS clearance.
- Smart exosomes peptide has the ability to mediate reduction of macrophage phagocytosis
- Smart exosomes drug delivery enhances cytotoxicity to PDAC cells
- In-vivo data available.
IP Status: Patent Pending
Publications: Genetically engineered exosomes enable active pancreatic cancer targeting and evading mononuclear phagocytic system