Smart Biomaterials as Immunomodulators in Cancer Therapy.

The integration of immunotherapy into oncology has transformed cancer treatment by harnessing the immune system to selectively eliminate malignant cells. Despite remarkable advances, conventional immunotherapies remain constrained by limited response rates, tumour heterogeneity and severe systemic toxicities, including cytokine release syndrome and autoimmunity. To address these challenges, smart biomaterials have emerged as next-generation platforms capable of modulating immune responses with high precision. By enabling localised and controlled release of therapeutic agents, these systems enhance drug retention at tumour sites, reduce systemic exposure and minimise off-target effects. Engineered biomaterials, including liposomes, polymeric nanoparticles, hydrogels, microneedle arrays and implantable scaffolds, provide spatial and temporal control over the delivery of cytokines, checkpoint inhibitors, engineered T cells and cancer vaccines. These platforms improve pharmacokinetics and biodistribution while also facilitating crosstalk with the tumour microenvironment, thereby enhancing therapeutic potency and reducing adverse effects. Recent innovations such as lipid nanoparticles for mRNA-based vaccines and reactive oxygen species-responsive hydrogels highlight the translational potential of these materials, with several formulations now advancing into clinical trials. This review synthesises current progress in the design and application of smart biomaterials as immunomodulators, emphasising their capacity to overcome major clinical barriers in cancer immunotherapy. Key areas of focus include strategies to improve immune cell recruitment, enhance antigen presentation and integrate multimodal therapies. By bridging materials science and immuno-oncology, smart biomaterials represent a transformative approach to achieving safer, more durable and personalised cancer treatments. Continued innovation in this field is poised to reshape the therapeutic landscape and accelerate clinical translation.