A Supramolecular Self‐Assembling Nanoagent by Inducing Intracellular Aggregation of PSMA for Prostate Cancer Molecularly Targeted Theranostics

Abstract Prostate cancer (PCa) with prostate‐specific membrane antigen (PSMA)‐specific high expression is well suited for molecularly targeted theranostics. PSMA expression correlates with the malignancy of PCa, and its dimeric form can promote tumor progression by exerting enzymatic activity to activate downstream signal transduction. However, almost no studies have shown that arresting the procancer signaling of the PSMA receptors themselves can cause tumor cell death. Meanwhile, supramolecular self‐assembling peptides are widely used to design anticancer agents due to their unique and excellent properties. Here, a PSMA‐targeting supramolecular self‐assembling nanotheranostic agent, DBT‐2FFGACUPA, which actively targets PSMA receptors on PCa cell membranes and induces them to enter the cell and form large aggregates, is developed. This process not only selectively images PSMA‐positive tumor cells but also suppresses the downstream procancer signals of PSMA, causing tumor cell death. This work provides an alternative approach and an advanced agent for molecularly targeted theranostics options in PCa that can induce tumor cell death without relying on any reported anticancer drugs.