Stimuli-responsive nanomaterials for the precision delivery of mRNA cancer vaccines

mRNA vaccines have emerged as a transformative platform for cancer immunotherapy, offering rapid design, scalable production, and the capacity to encode multiple tumor antigens. By delivering mRNA directly or via ex vivo transfected dendritic cells (DCs), these vaccines induce potent polyclonal immune responses and bypass HLA restrictions, enabling broad applicability across diverse patient populations. A central challenge remains the efficient and tumor-specific delivery of mRNA. Advanced nanocarriers have improved mRNA stability, cellular uptake, and antigen expression, while stimuli-responsive nanomaterials add precision by enabling controlled release triggered by tumor-specific cues. This approach minimizes systemic toxicity and enhances therapeutic efficacy. Preclinical studies consistently demonstrate strong antitumor responses, and early clinical efforts increasingly focus on cancer-associated antigen (CAA) vaccines and DC-based strategies. Future development must focus on optimizing delivery platforms for safety, efficiency, and large-scale manufacturing, while systematically identifying tumor-specific antigens and neoantigens for personalized vaccines. Combining mRNA vaccines with immune checkpoint inhibitors, cytokine therapies, or adoptive cell therapies may further overcome immunosuppressive tumor microenvironments (TME) and amplify clinical benefit. In parallel, standardized immunomonitoring and long-term evaluation of immune responses are essential for successful translation. Addressing these scientific and manufacturing challenges will accelerate the integration of stimuli-responsive nanomaterials into mRNA vaccine platforms, paving the way for next-generation cancer immunotherapies with greater precision, potency, and accessibility.