Targeting prostate cancer cells with a multivalent PSMA inhibitor-guided streptavidin conjugate

Tiancheng Liu, Jessie R. Nedrow-Byers, Mark R. Hopkins, Lisa Y. Wu, Jeonghoon Lee, Peter T.A. Reilly, Clifford E. Berkman

Research output: Contribution to journalArticle

Abstract

Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, its high expression is associated with prostate cancer progression, and has been becoming an active target for imaging or therapeutic applications for prostate cancer. On the other hand, streptavidin-biotin system has been successfully employed in pretargeting therapy towards multiple cancers. Herein, we describe the synthesis of bifunctional ligands (biotin-CTT54, biotin-PEG 4-CTT54, and biotin-PEG12-CTT54) possessing two functional motifs separated by a length-varied polyethylene glycol (PEG) spacer: one (CTT54) binds tumor-marker PSMA and the other (biotin) binds streptavidin or avidin. All three compounds exhibited high potencies (IC50 values: 1.21, 2.53, and 10 nM, respectively) and irreversibility; but only biotin-PEG12-CTT54 demonstrated specifically labeling PSMA-positive prostate cancer cells in a two-step pretargeting procedure. Additionally, the pre-formulated complex between biotin-PEG12-CTT54 and Cy5-streptavidin displayed the improved inhibitory potency (IC50 = 1.86 nM) and irreversibility against PSMA and rapid uptake of streptavidin conjugate into PSMA-positive prostate cancer cells through PSMA-associated internalization. Together, all these results supported a proof-concept that combination of streptavidin and PSMA's biotinylated inhibitor may lead to development of a novel strategy of tumor-targeting imaging or drug delivery towards prostate cancer.

Original languageEnglish (US)
Pages (from-to)3931-3934
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number12
DOIs
StatePublished - Jun 15 2012
Externally publishedYes

Keywords

  • Biotinylated PSMA inhibitor
  • Prostate cancer
  • Streptavidin-biotin system
  • Tumor-targeting imaging

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Targeting prostate cancer cells with a multivalent PSMA inhibitor-guided streptavidin conjugate'. Together they form a unique fingerprint.

Cite this