PSMA-Targeted Liposomes for Therapeutic Delivery into a Prostate Cancer Cell Model

Background: Prostate cancer (PCa) remains a significant health challenge, requiring innovative treatments. Here, we evaluated the efficacy of Talazoparib-loaded liposomes incorporating a targeting moiety, in combination with BI 2536, in PCa. This study develops lipid nanoparticles (LIPOs) targeting prostate-specific membrane antigen (PSMA) for better drug delivery. Methods: Two new PSMA-targeting agents, DUPA-DSPE and DUPA-PEG-DSPE, were created and incorporated into LIPOs via thin-film hydration. LIPOs' size and morphology were characterized using Dynamic light scattering, and structural analysis was done via TEM imaging. In vitro cytotoxicity and cell viability were assessed using an MTT assay, while in vivo radioactivity was evaluated by PET imaging, and radioactive activity was quantified using a γ-counter. Results: These LIPOs demonstrated excellent stability and specific binding to PSMA-expressing prostate cancer cells in vitro. In vivo, mouse model studies showed that PSMA-targeted LIPOs accumulated preferentially at tumor sites. Talazoparib, a PARP inhibitor with low solubility and cytotoxicity, has limited use in PCa. Conclusions: These findings provide proof-of-concept evidence that PSMA-targeted DUPA-PEG LIPOs can facilitate Talazoparib delivery and, particularly in combination with BI 2536, may enhance antitumor activity in PCa models. Further studies with expanded control groups and larger cohorts are warranted to validate the therapeutic efficacy of this combination strategy and support its further development for PCa treatment.