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Long-Circulating Prostate-Specific Membrane Antigen-Targeted NIR Phototheranostic Agent.

Marta Overchuk1,2, Martha P F Damen1,3, Kara M Harmatys1

  • 1Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Photochemistry and Photobiology
|November 20, 2019
PubMed
Summary

This study introduces a new bacteriochlorophyll-based photosensitizer for targeted photodynamic therapy (PDT) and imaging of prostate cancer. The agent effectively targets prostate-specific membrane antigen (PSMA) expressing tumors, enabling precise image-guided treatment.

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Area of Science:

  • Biomedical Engineering
  • Oncology
  • Photochemistry

Background:

  • Targeted photodynamic therapy (PDT) offers precision cancer treatment.
  • Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer, making it a key therapeutic target.
  • Near-infrared (NIR) light offers tissue penetration for advanced PDT.

Purpose of the Study:

  • To develop a novel bacteriochlorophyll-based photosensitizer for PSMA-targeted PDT and NIR fluorescence imaging.
  • To evaluate the targeting selectivity, pharmacokinetics, and therapeutic efficacy of the developed agent.
  • To assess its potential for image-guided surgical resection in PSMA-expressing tumors.

Main Methods:

  • Development of a tripartite bacteriochlorophyll-based photosensitizer (BPP) with a PSMA-affinity ligand and a D-peptide linker.
  • In vivo evaluation of BPP's PSMA-targeting selectivity in subcutaneous and orthotopic mouse models.
  • Assessment of BPP's pharmacokinetic properties, tumor accumulation, and PDT efficacy in a prostate adenocarcinoma mouse model.

Main Results:

  • BPP demonstrated excellent PSMA-targeting selectivity in preclinical models.
  • The D-peptide linker resulted in a prolonged plasma circulation time of 12.65 hours.
  • Effective tumor accumulation and potent PDT efficacy were observed in a prostate cancer mouse model.
  • Bright NIR fluorescence facilitated image-guided surgical resection.

Conclusions:

  • The developed bacteriochlorophyll-based PSMA-targeted photosensitizer (BPP) is a promising agent for image-guided photodynamic therapy and surgical resection of PSMA-expressing tumors.
  • BPP combines effective targeting, favorable pharmacokinetics, and potent PDT activity for precise cancer treatment.
  • Its NIR fluorescence capability enhances image guidance for surgical applications.