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 (99m)Tc 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 (18)F radionuclide. We found that the uptake of (99m)Tc-labeled P(3)-liposomes by LNCaP cells was >3-fold higher than (99m)Tc-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 IC(50) value of doxorubicin-loaded P(3)-liposomes was reduced by ~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.