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

Abstract The present work describes 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, our study indicates that the engineered anti-PSMA peptide-targeted EMs can be a promising drug delivery system for advanced PC.