Engineering Multimodal Nanomaterials for Prostate Cancer Theranostics: Design Principles, Recent Advances, and Translational Challenges.

Prostate cancer (PCa) remains a major clinical challenge because of limitations in early detection, tumor heterogeneity, therapeutic resistance, and metastatic progression. Nanomaterials provide versatile platforms for PCa theranostics by integrating molecular imaging, biomarker detection, targeted delivery, multimodal therapy, and therapeutic response assessment. This review summarizes recent advances in major nanomaterial platforms for PCa theranostics, including lipid-based nanomaterials, polymeric nanoparticles, gold nanoparticles (AuNPs), magnetic nanoparticles (MNPs), biomimetic nanoplatforms, and emerging smart nanocarriers, with emphasis on imaging enhancement, biosensing and liquid biopsy, targeted drug and nucleic acid delivery, phototherapy, sonodynamic and chemodynamic therapy (CDT), immunotherapy, and multimodal combination strategies. These advances reflect a shift from conventional single-function nanocarriers toward engineered multimodal theranostic systems that integrate molecular targeting, stimulus-responsive release, image-guided intervention, combination therapy, and therapeutic response monitoring. Unlike previous reviews that mainly describe nanomaterial categories or isolated applications, this review adopts an engineering-oriented design-function-application-translation framework to clarify how material properties, targeting strategies, and stimulus-responsive designs influence diagnostic performance, therapeutic selectivity, and clinical feasibility. Particular emphasis is placed on prostate-specific membrane antigen (PSMA)-targeted nanoplatforms as representative systems for theranostic integration. Current evidence suggests that nanoplatforms can improve tumor-selective accumulation, imaging sensitivity, biomarker detection, cargo stability, and intracellular delivery while reducing off-target toxicity. However, clinical translation remains limited by heterogeneous biodistribution, protein corona effects, nonspecific uptake, insufficient long-term biosafety data, manufacturing complexity, and batch-to-batch variability. Overall, nanomedicine may support more precise, minimally invasive, and integrated PCa management, but successful translation will require standardized characterization, scalable manufacturing, rigorous safety evaluation, clinically relevant validation, and rational integration with established diagnostic and therapeutic pathways.