Compounds for non-lethal micropinocytosis and exosome production

Project ID:  D2017-25

Background

Exosomes are vesicles in the range of 30 to 120nm, which are released from mammalian cells when multi-vesicular endosomes fuse with the plasma membrane. In recent times, exosomes have been implicated in cancer. Mounting evidence suggests that exosomes play an important role in mediating intercellular communication within the tumor microenvironment and promoting cancer invasion and metastasis. Exosomes have also attracted major attention as potential drug and therapeutic nano-carriers.  It would, therefore, be very important to develop compounds that are able to stimulate or inhibit the production of exosomes without affecting cell growth or viability.  Additionally, macropinocytosis is a distinct vesicular transport process that cells use to internalize fluid from the extracellular environment. Recently, attention has been drawn to the possibility that stimulation of macropinocytosis may enhance the uptake of chemotherapeutic agents by cancer cells.

Invention Description

Researchers at the University of Toledo, led  by Dr. William Maltese, have developed small molecules that can both a) increase the production of exosomes by cells and b) stimulate macropinocytosis, without short-term impairment of cell viability.

Applications

• Exosomes may be used as drug and RNA therapeutic delivery vehicles
• The exosomes may be used as diagnostics to track tumor occurrence and progression
• Stimulation of macropinocytotic uptake of drugs

Advantages

• Cell proliferation and viability are not impaired by the compounds.
• Compared to controls the characteristics of exosomes from treated cells showed no significant difference.

IP Status:             Patent pending, Publication No. 2021-0038586

Publications:      1.           Li Z Mbah N, Maltese W, Vacuole-inducing compounds that disrupt endolysosomal trafficking stimulate production of exosomes by glioblastoma cells. Mol Cell Biochem. 2018 February; 439(1-2): 1–9.

                              2.          Colin M, et al., Dysregulation of Macropinocytosis Processes in Glioblastomas May Be Exploited to Increase Intracellular Anti-Cancer Drug Levels: The Example of Temozolomide.  Cancers 2019, 11, 411;