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Related Experiment Video

Updated: May 2, 2026

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
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A small-molecule pretargeting approach for PSMA-targeted conjugates.

Nooshin Mesbahi1, Hosog Yoon1, Melody D Fulton1

  • 1Washington State University, Department of Chemistry Pullman, WA 99164-4630, United States.

Bioorganic & Medicinal Chemistry Letters
|March 30, 2025
PubMed
Summary
This summary is machine-generated.

We developed a pretargeting strategy for targeted prostate cancer cell delivery using a PSMA-targeted ligand and click chemistry. This approach enhances the specificity and safety of cancer treatments.

Keywords:
PSMAPSMA targeted moleculePhosphoramidatePretargeting

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Prostate cancer remains a leading cause of cancer death.
  • Targeted delivery of payloads to cancer cells can improve treatment efficacy.
  • Prostate-specific membrane antigen (PSMA) is a key biomarker for prostate cancer.

Purpose of the Study:

  • To develop and validate a pretargeting approach for targeted delivery of molecular payloads to PSMA-expressing prostate cancer cells.
  • To assess the feasibility of using click chemistry for enhanced specificity in payload delivery.

Main Methods:

  • Development of a phosphoramidate-based PSMA ligand (CTT1298) functionalized with a DBCO group.
  • Utilizing strain-promoted azide-alkyne cycloaddition (SPAAC) for payload conjugation.
  • Employing 6-FAM-Azide as a model fluorescent payload for delivery studies.

Main Results:

  • PSMA-targeted probe (FAM-C6-1298) demonstrated successful delivery and accumulation in PSMA+ cells.
  • Live-cell experiments confirmed selective pretargeted delivery of the payload using DBCO-C6-1298 and 5-FAM-azide.
  • The pretargeting strategy showed high specificity for PSMA+ cells.

Conclusions:

  • The developed pretargeting strategy is feasible for PSMA+ prostate cancer cells.
  • This approach holds potential for preclinical applications in targeted cancer therapy and diagnostics.
  • The method enhances specificity and safety in prostate cancer treatment delivery.