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

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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 (LNPs) 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 LNPs via thin-film hydration. LNPs’ 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 LNPs demonstrated excellent stability and specific binding to PSMA-expressing prostate cancer cells in vitro. In vivo, mouse model studies showed that PSMA-targeted LNPs accumulated preferentially at tumor sites. Talazoparib, a PARP inhibitor with low solubility and cytotoxicity, has limited use in PCa. Conclusions: Loading Talazoparib into DUPA-PEG LNPs significantly improved its therapeutic effect, especially when combined with BI2536. PSMA-targeted LNPs enhanced drug delivery and treatment efficacy for PCa. Further research is needed to optimize formulations and explore additional combination therapies for clinical use. This work highlights the potential of targeted delivery systems to advance PCa treatments.

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