Enzymatic activation of a doxorubicin-peptide prodrug by prostate-specific antigen.

Synthesis and biological evaluation of an albumin-binding prodrug of doxorubicin that is cleaved by prostate-specific antigen (PSA) in a PSA-positive orthotopic prostate carcinoma model (LNCaP).

The prostate-specific antigen (PSA) is a serine protease that is over-expressed in prostate carcinoma and represents a molecular target for selectively releasing an anticancer agent from a prodrug formulation. We have recently investigated a macromolecular prodrug strategy for improved cancer chemotherapy based on 2 features: (i) rapid and selective binding of thiol-reactive prodrugs to the cys...

PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites.

Tumor-selective delivery of doxorubicin by a prostate-specific antigen (PSA)-targeted peptide conjugate prodrug of doxorubicin was demonstrated in a nude mouse xenograft model of human prostate cancer. The prodrug (referred to as doxorubicin conjugate) contains doxorubicin linked to a seven-amino acid peptide conjugate that was designed to increase delivery of doxorubicin to tumor sites through...

Engineered Jurkat Cells for Targeting Prostate-Specific Membrane Antigen on Prostate Cancer Cells by Nanobody-Based Chimeric Antigen Receptor

Background: Recently, modification of T cells with chimeric antigen receptor (CAR) has been an attractive approach for adoptive immunotherapy of cancers. Typically, CARs contain a single-chain variable domain fragment (scFv). Most often, scfvs are derived from a monoclonal antibody of murine origin and may be a trigger for host immune system that leads to the T-cell clearance. Nanobody is a spe...

Enzymatic Activation of Peptide Prodrugs by Prostate-Specific Membrane Antigen (PSMA) as Targeted Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR:

A prostate-specific antigen activated N-(2-hydroxypropyl) methacrylamide copolymer prodrug as dual-targeted therapy for prostate cancer.

Prostate cancer targeted peptide prodrugs that are activated by the serine protease activity of prostate-specific antigen (PSA) are under development in our laboratory. To enhance delivery and solubility of these prodrugs, macromolecular carriers consisting of N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers were covalently coupled to a PSA-activated peptide prodrug. HPMA copolymers a...