Nanomedicine-based cancer immunotherapy: translational barriers, mechanistic strategies, and future perspectives.

Nanomedicine-based cancer immunotherapy integrates nanotechnology with immune modulation, representing a promising strategy to improve both the efficacy and safety of cancer treatment. Despite substantial preclinical potential, clinical translation is hindered by interconnected challenges in pharmacology, pharmacodynamics, and long-term safety. This mechanism-oriented prospective analyzes translational bottlenecks, pharmacological uncertainty from biomolecular corona, suboptimal pharmacodynamics due to tumor barriers, and metabolism/excretion affecting biosafety. Using a concept-driven framework, we link nano-bio interactions to clinical outcomes within a 'barrier-strategy' paradigm. Corresponding strategies such as mechanism-driven design, AI-assisted optimization, and advanced delivery systems are discussed, with emphasis on safety-by-design principles. Collectively, this perspective provides a forward-looking roadmap for future research, underscoring the importance of integrated technologies, advanced translational models, and scalable manufacturing to fully realize the clinical potential of nanoimmunotherapy.