Hyaluronic acid-based strategies for prostate cancer therapy.

Hyaluronic acid (HA) has emerged as a pivotal biomaterial in prostate cancer management, bridging the gap between physical tissue spacing and targeted molecular therapy. While HA-based hydrogels are clinically established, and nanomedicines are rapidly evolving, a comprehensive integration of these distinct domains remains lacking. This review critically synthesizes the dual roles of HA in prostate cancer radiotherapy and drug delivery. We first delineate the biological basis of HA, emphasizing its interactions with CD44/RHAMM receptors and the implications for material design. Clinically, we systematically evaluate the efficacy of HA hydrogel spacers across diverse radiotherapy modalities, including SBRT, brachytherapy, and hypofractionated regimens, highlighting their quantitative impact on prostate-rectum separation and the substantial reduction of gastrointestinal toxicity. Beyond physical spacing, we analyze the translational status of HA-based nanocarriers, discussing their potential to overcome drug resistance through receptor-mediated active targeting. Crucially, we address significant limitations in current strategies, such as the structural heterogeneity arising from imprecise chemical modifications and the lack of standardized in vivo stability evaluation systems. Finally, we propose a roadmap for future research, advocating for subtype-specific material design, the development of intelligent stimuli-responsive derivatives, and synergy with emerging immunotherapies to realize precision medicine in prostate cancer.