PSMA‐Targeting Imprinted Nanogels for Prostate Tumor Localization and Imaging

Abstract

Prostate‐specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and tumor vasculature, making it an important biomarker. However, conventional PSMA‐targeting agents like antibodies and small molecules have limitations. Antibodies exhibit instability and complex production, while small molecules show lower specificity and higher toxicity. Herein, this work develops a novel PSMA‐targeting synthetic antibody to address prior limitations. This work synthesizes fluorescently labelled, N‐isopropylacrylamide‐based epitope imprinted nanogels (MIP‐M) using a dispersion of magnetic nanoparticles as template carriers with a linear epitope from PSMA's extracellular apical domain as the template. MIP‐M demonstrates high binding affinities for both the epitope template (apparent KD = 6 × 10−10 м) and PSMA (apparent KD = 2.5 × 10−9 м). Compared to reference peptides and human serum albumin, MIP‐M indicates high specificity. Flow cytometry and confocal laser scanning microscopy comparing cell lines displaying normal (PC3) and enhanced (LNCaP) PSMA expression levels, revealed that MIP‐M and a PSMA antibody exhibits comparable binding preferences for the latter cell line. Moreover, MIP‐M demonstrates selectivity on par with the PSMA antibody for targeting PSMA‐positive prostate tumor over normal tissue, enabling discrimination. This MIP‐M addresses stability, production, specificity and toxicity limitations of prior targeting agents and offer a promising alternative for PSMA‐directed cancer diagnosis and treatment.