PSMA-Targeting Imprinted Nanogels for Prostate Tumor Localization and Imaging

• Published in: Advanced healthcare materials 2024-12, p.e2401929
• Main Authors: Zhang, Tong, Berghaus, Melanie, Li, Yuan, Song, Qingmei, Stollenwerk, Maria M, Persson, Jenny, Shea, Kenneth J, Sellergren, Börje, Lv, Yongqin
• Format: Article
• Language: English
• Subjects: dispersed‐phase imprinting; molecularly imprinted nanogels; prostate cancer; prostate‐specific membrane antigen; tissue imaging
• ISSN: 2192-2659; 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202401929

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 K = 6 × 10 м) and PSMA (apparent K = 2.5 × 10 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.