Research Projects

Extracellular vesicles (EVs) are crucial for inter-cellular communication and serve as potential biomarkers for diseases. They have been used in therapy due to their high stability in circulation and targeting ability to desired organs. However, there are limitations to EVs' use for drug delivery, such as the potential neutralization by immune cells. Neutrophil-derived EVs, which are a large fraction of EVs present in circulation, could be used for drug delivery. The researchers propose to isolate neutrophil-derived EVs, which are spontaneously released without an inflammatory response, and use them for drug delivery. The hypothesis is that these EVs might enable higher internalization in recipient immune cells, leading to better responses to diseases. One specific application is the delivery of single-chain fragment variable (scFv) for PD-1 (programmed death receptor), potentially developing a new immunotherapeutic. To achieve this, the researchers plan to in-vitro transcribe mRNA encoding for the scFv of PD-1 and encapsulate it into the neutrophil-derived EVs. These EVs will then be delivered to neutrophils in the tumor microenvironment to produce PD-1-like protein to bind to the PD-L1 ligand produced by cancer cells. This is intended to reverse the effect of cancer-cell mediated inhibition of T cell cytolysis. The researchers plan to test this phenomenon in mice breast cancer models where they want to deliver EVs and check the reversal of tumor growth. This will provide a translational approach to overcoming barriers in EV-immune cell interaction.

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