English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Cytoplasmic localization of prostate-specific membrane antigen inhibitors may confer advantages for targeted cancer therapies

Matthias, J., Engelhardt, J., Schäfer, M., Bauder-Wüst, U., Meyer, P. T., Haberkorn, U., et al. (2021). Cytoplasmic localization of prostate-specific membrane antigen inhibitors may confer advantages for targeted cancer therapies. Cancer Research, 81(8), 2234-2245. doi:10.1158/0008-5472.CAN-20-1624.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files
hide Files
:
3348953.pdf (Publisher version), 2MB
 
File Permalink:
-
Name:
3348953.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), MBPC; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Matthias, J., Author
Engelhardt, J., Author
Schäfer, M., Author
Bauder-Wüst, U., Author
Meyer, P. T., Author
Haberkorn, U., Author
Eder, M., Author
Kopka, K., Author
Hell, S. W.1, Author              
Eder, A.-C., Author
Affiliations:
1Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society, ou_578627              

Content

show
hide
Free keywords: -
 Abstract: Targeted imaging and therapy approaches based on novel prostate-specific membrane antigen (PSMA) inhibitors have fundamentally changed the treatment regimen of prostate cancer. However, the exact mechanism of PSMA inhibitor internalization has not yet been studied, and the inhibitors' subcellular fate remains elusive. Here, we investigated the intracellular distribution of peptidomimetic PSMA inhibitors and of PSMA itself by stimulated emission depletion (STED) nanoscopy, applying a novel nonstandard live cell staining protocol. Imaging analysis confirmed PSMA cluster formation at the cell surface of prostate cancer cells and clathrin-dependent endocytosis of PSMA inhibitors. Following the endosomal pathway, PSMA inhibitors accumulated in prostate cancer cells at clinically relevant time points. In contrast with PSMA itself, PSMA inhibitors were found to eventually distribute homogeneously in the cytoplasm, a molecular condition that promises benefits for treatment as cytoplasmic and in particular perinuclear enrichment of the radionuclide carriers may better facilitate the radiation-mediated damage of cancerous cells. This study is the first to reveal the subcellular fate of PSMA/PSMA inhibitor complexes at the nanoscale and aims to inspire the development of new approaches in the field of prostate cancer research, diagnostics, and therapeutics. SIGNIFICANCE: This study uses STED fluorescence microscopy to reveal the subcellular fate of PSMA/PSMA inhibitor complexes near the molecular level, providing insights of great clinical interest and suggestive of advantageous targeted therapies.

Details

show
hide
Language(s): eng - English
 Dates: 2021-02-232021-04-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1158/0008-5472.CAN-20-1624
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Cancer Research
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 81 (8) Sequence Number: - Start / End Page: 2234 - 2245 Identifier: -