Development of In Vitro Prostate Cancer Biomarkers on the Basis of Gelatin Matrix Incorporated Gold Nanoparticles Functionalized with Fluorescence Dye and Prostate Specific Membrane Antigen

摘要

It's known that prostate-specific membrane antigen (PSMA) is one of the most well established and highly specific prostate epithelial cell membrane antigens. PSMA is a type II transmembrane zinc metallopeptidase, belonging to the M28 peptidase family. It possesses hydrolyzing enzyme activities and is also known as FOLH1 (foliate hydrolase 1). The combination of a nanoparticle platform with targeting ligands for tumor cell-surface biomarkers is a promising architecture for achieving selective drug delivery and uptake into target cells. Gold nanoparticles (GNPs) are prone to be attached to many biological probes such as antibodies, enzymes, lectins, glycans, nucleic acids, and receptors. In this study as the prostate cancer (CaP) biomarker, we propose GNPs functionalized with PSMA and fluorescent dyes. We have investigated a possibility to obtain an increased fluorescence signal, gained from GNPs conjugated with fluorescent dye and PSMA. The electric charge on the GNPs, the distance between GNPs and luminescent dye molecules has a significant effect on the luminescence intensity, and this enhancement highly depends upon the excitation wavelength of pumping laser source. Charged antigen, such as PSMA, can absorb on GNPs via electrostatic interaction. As the in vitro platform, we have used a biotissue mimicking phantoms based on gelatin matrix. Gelatin-based materials are attractive due to their stable mechanical properties and ease of fabrication. Proposed method that is specific and reliable for detecting cancers at early stages and is easily accessible so that it can function as the first-line guidance is of utter importance. Further, the unique physical properties of developed nanoscale materials can be utilized to produce novel and effective sensors for cancer diagnosis, agents for tumor imaging, and therapeutics for treatment of cancer.