Surface Modification of Liposomes by a Lipopolymer Targeting Prostate Specific Membrane Antigen for Theranostic Delivery in Prostate Cancer.

Prostate specific membrane antigen (PSMA) is a marker for diagnosis and targeted delivery of therapeutics to advanced/metastasized prostate cancer. We report a liposome-based system for theranostic delivery to PSMA-expressing (PSMA(+)) LNCaP cells. A lipopolymer (P-3) comprising of PSMA ligand (PSMAL), polyethylene glycol (PEG(2000)), and palmitate was synthesized and post-inserted into the surface of preformed liposomes. These P-3-liposomes were loaded with doxorubicin and radiolabeled with Tc-99m radionuclide to study their theranostic characteristics. Differential expression of PSMA on LNCaP and PC3 cells was confirmed by immunoblotting as well as by uptake of PSMAL labeled with F-18 radionuclide. We found that the uptake of Tc-99m-labeled P-3-liposomes by LNCaP cells was >3-fold higher than Tc-99m-labeled Plain-liposomes; the amount of doxorubicin delivered to LNCaP cells was also found to be >3-fold higher by P-3-liposomes. Cell-based cytotoxicity assay results showed that doxorubicin-loaded P-3-liposomes were significantly more toxic to LNCaP cells (p < 0.05), but not to PSMA-negative PC3 cells. Compared to doxorubicin-loaded Plain-liposomes, the IC50 value of doxorubicin-loaded P-3-liposomes was reduced by similar to 5-fold in LNCaP cells. Together, these results suggest that surface functionalization of liposomes with small PSMA-binding motifs, such as PSMAL, can provide a viable platform for specific delivery of theranostics to PSMA(+) prostate cancer.