Novel composite nano-frameworks for prostate cancer therapy <i>via</i> synergistic targeting of ribonucleotide reductase

Prostate cancer, a common malignancy in men, poses significant clinical challenges, especially as it progresses to castration-resistant prostate cancer (CRPC). Conventional therapies become less effective due to acquired drug resistance, and even enzalutamide (ENZR), a cornerstone treatment for CRPC, eventually faces resistance. Understanding the clinical significance of ENZR resistance is crucial for improving prostate cancer treatment. To address this issue, we developed an innovative nanosystem: Deferasirox (DEF)-loaded self-etched platinum-cobalt nanodendrites encapsulated within a nanoframe (Pt/Co-ND@DEF). This system combines chemodynamic therapy (CDT) with DEF delivery. Pt/Co-ND@DEF demonstrates potent peroxidase-like activity, catalyzing hydrogen peroxide (H 2 O 2 ) decomposition and glutathione (GSH) depletion to generate reactive oxygen species (ROS). Additionally, DEF release reduces tumor iron ion (Fe 3+ ) content, disrupting ribonucleotide reductase activity essential for DNA synthesis and arresting the cell cycle. This dual-action mechanism enhances ROS-induced cytotoxicity and boosts ENZR’s efficacy against CRPC, offering a promising multi-target strategy. Our study represents a significant step forward in overcoming ENZR resistance and enhancing prostate cancer treatment, providing new therapeutic avenues for advanced cases.