Genetically-engineered anti-PSMA exosome mimetics targeting advanced prostate cancer in vitro and in vivo

Researchers from Queen’s University Belfast describe the engineering of anti-PSMA peptide-decorated exosome mimetics (EMs) targeting advanced prostate cancer (PC). The targeted EMs were produced from anti-PSMA peptide, WQPDTAHHWATL, expressing U937 monoblastic cells, followed by successive extrusion cycles. The engineered EMs were nanosized, produced at a high yield, and displayed the anti-PSMA peptide, exosomal markers and monocytes proteins on their surface. As anticipated, PSMA-EMs showed increased cellular internalization in PSMA positive PC cell lines (LNCaP and C4-2B), compared to unmodified EMs. Most importantly, higher tumour targeting was observed in solid C4-2B tumours, following intravenous administration, confirming their targeting ability in vivo. Overall, this study indicates that the engineered anti-PSMA peptide-targeted EMs can be a promising drug delivery system for advanced PC.

 

Monoblastic U937 cells were transfected by nucleofection to express the PSMA targeting peptide on their membrane surface. The cells were extruded to produce the PSMA-targeted exosome mimetics with active targeting properties and improved internalization in PSMA expressing tumour in vitro and in vivo.

Severic M, Ma G, Pereira S, Ruiz A, Cheung CCL ,Al-Jamal WT. (2020) Genetically-engineered anti-PSMA exosome mimetics targeting advanced prostate cancer in vitro and in vivo. J of Cont Rel [Epub ahead of print]. [abstract]

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