4.8 Article

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

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 330, Issue -, Pages 101-110

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2020.12.017

Keywords

Prostate cancer; Prostate-specific membrane antigen; Active targeting; Exosome mimetics

Funding

  1. Rosetrees Trust studentship 2016-2019 [M542]
  2. Prostate Cancer UK [CDF12-002]
  3. Engineering and Physical Sciences Research Council (EPSRC) [EP/M008657/1]
  4. EPSRC [EP/M008657/1] Funding Source: UKRI

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The engineered anti-PSMA peptide-targeted EMs showed increased cellular internalization in PSMA positive PC cell lines and higher tumor targeting ability in vivo, indicating their potential as a promising drug delivery system for advanced prostate cancer.
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.

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