Engineering mesoporous silica nanoparticles for cancer immunotherapy: mechanistic insights, therapeutic synergies, and translational roadmap

• Mesoporous silica nanoparticles actively stimulate immune cells beyond acting as carriers. • They enable synergy by combining antigen delivery, immune modulation, and triggered therapies. • They can deliver messenger ribonucleic acid vaccines and gene-editing tools to reshape the tumor microenvironment. • The review outlines key challenges in safety, manufacturing, and translation compared to advanced nanocarriers. Cancer immunotherapy has revolutionized oncology but remains constrained by the immunosuppressive tumor microenvironment (TME), systemic toxicities, and inadequate delivery of biologic agents. Nanotechnology offers a promising avenue to overcome these hurdles, with mesoporous silica nanoparticles (MSNs) emerging as a particularly versatile platform. This review comprehensively analyzes the application of MSNs in advancing cancer immunotherapy. We begin by outlining the current landscape of immunotherapies and their limitations. We then delve into the unique physicochemical properties of MSNs, and their direct impact on immune cell engagement and intrinsic adjuvanticity. The core of the review details strategic MSN-based approaches for innate and adaptive immune reprogramming, including antigen/danger signal co-delivery, surface engineering for targeted delivery, and combination with modalities like photodynamic/photothermal therapy to induce immunogenic cell death. Furthermore, we explore high-impact, underexplored frontiers such as MSN-mediated delivery of mRNA vaccines and CRISPR-Cas9 machinery for TME reprogramming. Finally, we critically assess the translational pathway, identifying key bottlenecks in safety, manufacturing, and regulatory approval, while providing a preclinical roadmap and a comparative analysis against clinical-stage nanocarriers. This synthesis underscores the potential of MSNs not merely as passive carriers, but as active, multifunctional immunomodulatory platforms poised to enhance the efficacy and specificity of next-generation cancer immunotherapies.