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

Maja Severic; Guanglong Ma; Sara G T Pereira; Amalia Ruiz; Calvin C L Cheung; Wafa T Al-Jamal

doi:10.1016/j.jconrel.2020.12.017

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

Maja Severic
, Guanglong Ma
, Sara G T Pereira
, Amalia Ruiz
, Calvin C L Cheung
, Wafa T Al-Jamal

Research output: Contribution to journal › Article › peer-review

54 Citations (Scopus)

683 Downloads (Pure)

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.

Original language	English
Pages (from-to)	101-110
Number of pages	10
Journal	Journal of controlled release : official journal of the Controlled Release Society
Volume	330
Early online date	14 Dec 2020
DOIs	https://doi.org/10.1016/j.jconrel.2020.12.017
Publication status	Published - Feb 2021

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.jconrel.2020.12.017Licence: Unspecified

Genetically-Engineered Anti-PSMA Exosome Mimetics Targeting Advanced Prostate Cancer In Vitro and In Vivo
© 2020 Elsevier B. V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/,which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Accepted author manuscript, 1.39 MBLicence: CC BY-NC-ND

Engineering PSMA-targeted exosome-like vesicles to target prostate cancer metastasis
Severic, M. (Author), Al-Jamal, W. (Supervisor) & Burrows, J. (Supervisor), Dec 2022
Student thesis: Doctoral Thesis › Doctor of Philosophy

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title = "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.",

author = "Maja Severic and Guanglong Ma and Pereira, \{Sara G T\} and Amalia Ruiz and Cheung, \{Calvin C L\} and Al-Jamal, \{Wafa T\}",

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doi = "10.1016/j.jconrel.2020.12.017",

language = "English",

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T1 - Genetically-engineered anti-PSMA exosome mimetics targeting advanced prostate cancer in vitro and in vivo

AU - Severic, Maja

AU - Ma, Guanglong

AU - Pereira, Sara G T

AU - Ruiz, Amalia

AU - Cheung, Calvin C L

AU - Al-Jamal, Wafa T

PY - 2021/2

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AB - 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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DO - 10.1016/j.jconrel.2020.12.017

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JO - Journal of controlled release : official journal of the Controlled Release Society

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ER -

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

Abstract

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Student theses

Engineering PSMA-targeted exosome-like vesicles to target prostate cancer metastasis

Cite this