Exosomes are natural nanocarriers that play a significant role in intercellular communication and signaling processes. Depending on the type of parent cells, the secreted exosomes display distinctive biological function with the preservation of naïve properties of the parent cell. Towards this direction, we hypothesize that the immune cell-derived exosomes will preserve inherent immunogenic properties which can be further used for therapeutic application, for example, targeted drug delivery. However, the series of ultra-centrifuge based exosomes isolation result in lower yield limits its application, which is the major roadblock to implement exosomes in drug delivery. Herein, our overarching hypothesis is that by hybridizing exosomes with a synthetic liposome, a solution in drug delivery can be achieved by increasing the number of the hybrid exosome. Along this line, we re-engineered exosomes by integrating mouse macrophage (J774A.1) derived immuno exosomes with synthetic liposome following extrusion method. Formation of hybrid exosomes was monitored and confirmed by fluorescent resonance energy transfer (FRET), which showed diminished FRET effect due to the increased distance between two FRET pairs in hybrid exosomes. Furthermore, SDS-PAGE electrophoresis confirmed the successful translocation of surface protein markers from exosomes into the hybrid exosomes. An in vitro specificity of hybrid exosomes was studied with a mouse breast cancer cell (4T1) and human breast cancer cells MDA-MB-231 and MCF-7. Normal human breast (MCF-10A) and normal mouse fibroblast (NIH-3T3) cells were used as a normal control to evaluate the cancer cell specificity of the hybrid exosomes. Cellular internalization of hybrid exosomes was studied using flow cytometry and confocal imaging, which showed higher accumulation in cancer cell than that of normal cells. Moreover, the hybrid exosomes showed biocompatibility when tested with normal cells with more than 85% cellular viability. These results suggest that the engineered hybrid exosomes could be an exciting platform technology for tumor-targeted drug delivery.

Engineering immune cell-derived hybrid exosomes for tumor-targeted drug delivery

256th National Meeting (2018)

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