Prostate-Specific Membrane Antigen Targeted Gold Nanoparticles for Theranostics of Prostate Cancer

Abstract

Prostate cancer is one of the most common cancers and among the leading causes of cancer deaths in the United States. Men diagnosed with the disease typically undergo radical prostatectomy, which often results in incontinence and impotence. Recurrence of the disease is often experienced by most patients with incomplete prostatectomy during surgery. Hence, the development of a technique that will enable surgeons to achieve a more precise prostatectomy remains an open challenge. In this contribution, we report a theranostic agent (AuNP-5kPEG-PSMA-1-Pc4) based on prostate-specific membrane antigen (PSMA-1)-targeted gold nanoparticles (AuNPs) loaded with a fluorescent photodynamic therapy (PDT) drug, Pc4. The fabricated nanoparticles are well-characterized by spectroscopic and imaging techniques and are found to be stable over a wide range of solvents, buffers, and media. In vitro cellular uptake experiments demonstrated significantly higher nanoparticle uptake in PSMA-positive PC3pip cells than in PSMA-negative PC3flu cells. Further, more complete cell killing was observed in Pc3pip than in PC3flu cells upon exposure to light at different doses, demonstrating active targeting followed by Pc4 delivery. Likewise, in vivo studies showed remission on PSMA-expressing tumors 14 days post-PDT. Atomic absorption spectroscopy revealed that targeted AuNPs accumulate 4-fold higher in PC3pip than in PC3flu tumors. The nanoparticle system described herein is envisioned to provide surgical guidance for prostate tumor resection and therapeutic intervention when surgery is insufficient.

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

“…Nanoparticles represent an emerging technology in medicinal applications due their unique pharmacokinetic properties, amenability for multifunctionalization and high loading capacities [201]. With respect to PSMA-targeting, several types of nanoparticles have been outfitted with various types targeting agents (e.g., antibodies, aptamers, urea inhibitors) demonstrating their utility for in vitro and in vivo prostate cancer applications [202][203][204]. However, even though nanoparticles seem to be attractive platform for the development of multimodal theragnostic agents, not many nanoparticle-based radiopharmaceuticals for prostate cancer therapy have been reported.…”

Targeted Gold Nanocluster‐Enhanced Radiotherapy of Prostate Cancer

“…In clinical studies, Lutetium 177 (Lu) labeled PSMA peptides have already proved to be effective in targeted radionuclide therapy of prostate cancer . Recently, we have developed a high‐affinity PSMA targeting ligand (PSMA‐1) and demonstrated its use in prostate cancer imaging and photodynamic therapy . Here the PSMA‐1 ligand is further modified for in situ synthesis of PSMA‐1‐targeted Au 25 nanoclusters (CY‐PSMA‐1‐Au 25 NCs), providing a high affinity and highly effective radiosensitizer for prostate cancer that is also small enough to be excreted by the kidneys within hours.…”

Theranostic Nanoparticles and Their Spectrum in Cancer

“…PDTspecific nanoparticles are used as photosensitizer carriers [225,226]. Moreover, these nanocarriers can be functionalized with targeting ligands for better tumor selectivity and also with drug molecules for therapeutic effectiveness [227][228][229]. Gold nanoparticles loaded with a fluorescent drug Pc4 targeting PSMA-1 membrane antigen in prostate cancer are promising tools for surgical guidance and further therapeutic intervention [228].…”

“…Moreover, these nanocarriers can be functionalized with targeting ligands for better tumor selectivity and also with drug molecules for therapeutic effectiveness [227][228][229]. Gold nanoparticles loaded with a fluorescent drug Pc4 targeting PSMA-1 membrane antigen in prostate cancer are promising tools for surgical guidance and further therapeutic intervention [228]. EGFR-targeted liposomal nanohybrid cerasomes are proposed for PDT and immunotherapy in colorectal cancer due to their sensitive detection properties and anti-tumor efficacy [229].…”