Abstract
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 (P3) comprising of PSMA ligand (PSMAL), polyethylene glycol (PEG2000), and palmitate was synthesized and post-inserted into the surface of preformed liposomes. These P3-liposomes were loaded with doxorubicin and radiolabeled with 99mTc 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 18F radionuclide. We found that the uptake of 99mTc-labeled P3-liposomes by LNCaP cells was >3-fold higher than 99mTc-labeled Plain-liposomes; the amount of doxorubicin delivered to LNCaP cells was also found to be >3-fold higher by P3-liposomes. Cell-based cytotoxicity assay results showed that doxorubicin-loaded P3-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 P3-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.
Highlights
Prostate cancer is a leading cancer in men worldwide
These results suggest that surface functionalization of liposomes with small prostate specific membrane antigen (PSMA)-binding motifs, such as PSMA ligand (PSMAL), can provide a viable platform for specific delivery of theranostics to PSMA+ prostate cancer
The objective of this study was to develop theranostic liposomes loaded with doxorubicin, which are targeted to PSMA by surface modification with a PSMA-ligand (PSMAL)
Summary
Prostate cancer is a leading cancer in men worldwide. According to the Cancer Statistics 2017, there were 161,360 new cases and 26,730 projected deaths attributed to prostate cancer [1]. The overall 5-year survival rate of prostate cancer patients in the USA is 97.3%, it declines drastically to 29% in patients with advanced stage prostate cancer [2,3]. Early and accurate diagnosis of prostate cancer is vital to treatment success. Primary diagnosis of prostate cancer is usually based on circulating levels of prostate-specific antigen combined with digital rectal exam, which help identify cancer at earliest stages in screening methodologies; ultrasound, biopsy, and magnetic resonance imaging are employed to confirm the initial screening results
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