mRNA vaccine delivery strategies for cancer therapy

Cancer therapy is often lengthy and challenging, substantially affecting the quality of life and health of patients. mRNA cancer vaccines represent a novel strategy in cancer immunotherapy that work by activating the patient's immune system to target cancer cells through the delivery of mRNA encoding specific antigens. Compared with traditional chemotherapy, radiotherapy, and surgery, this new form of cancer immunotherapy offers improved therapeutic effects and reduced toxic side effects. Unlike DNA vaccines or viral vector-based vaccines, mRNA vaccines operate exclusively in the cytoplasm and do not integrate into the genome, thereby avoiding the potential risk of insertional mutations. Furthermore, mRNA vaccines are recognized for their short half-life, favorable biosafety, compatibility, and avoidance of T-cell depletion due to continuous antigen exposure. Nevertheless, challenges such as instability, autoimmunogenicity, and low delivery efficiency continue to limit their wider clinical application. Recent advancements in nanotechnology have opened new avenues for mRNA delivery. Designing mRNA cancer vaccine vectors involves careful consideration of factors such as size, composition, charge, and hydrophobicity to maximize drug loading and minimize immune rejection. Research shows that effective mRNA delivery strategies can improve the stability of mRNA, protect it from nuclease degradation, and improve cell transfection efficiency. Consequently, the formulation of optimized delivery strategies for mRNA vaccines is essential to enhance their therapeutic efficacy. This review explores the mechanism of action of mRNA vaccines first, then identifies potential issues with current mRNA vaccine delivery methods, and provides a systematic summary of delivery strategies using various carrier systems, including bio-derived, organic, inorganic, and hybrid composite nanomaterials, discussing their advantages and limitations. Moreover, different delivery routes, including various drug delivery modes and mRNA controlled-release strategies, are summarized. The administration of mRNA vaccines has been shown to effectively regulate antigen expression and modulate immune responses. Common approaches for cancer vaccine administration include intramuscular, intratumoral, intravenous, subcutaneous, and intradermal injections as well as noninvasive methods such as intranasal delivery. Different administration routes considerably influence organ distribution, expression kinetics, and therapeutic efficacy of the vaccine. Additionally, implementing an appropriate stimulus-responsive controlled-release strategy for mRNA vaccines can minimize inflammatory side effects and enhance safety. Given the unique characteristics of various tumor microenvironments, such as acidic pH values and elevated glutathione concentrations, a controlled-release system responsive to these cues can facilitate targeted vaccine delivery to tumor sites, improving the utilization efficiency of mRNA vaccines. Furthermore, external physical field-responsive mRNA vaccines can adapt their action timing and duration based on real-time treatment conditions, allowing for adjustments such as targeted aggregation and accelerated release to better address clinical needs in cancer therapy. Finally, this review addresses the current limitations and future prospects of mRNA cancer vaccines. mRNA vaccines have been developed for various diseases and have garnered significant attention and research in cancer therapy. Although mRNA-based monotherapy may be effective for early-stage cancer or as adjuvant therapy, advanced cancer often requires combination with other treatments for optimal results. It is anticipated that with ongoing advances in overcoming current challenges, mRNA cancer vaccines will become powerful resources in the fight against cancer. To facilitate clinical transition, researchers must investigate the role of mRNA vaccines from multiple perspectives and models; conduct comprehensive clinical trials to evaluate the vaccines' immunogenicity and safety; optimize dosage, treatment plans, and administration routes for different patient conditions; and validate practical vaccine administration methods. Tailoring treatment to individual patients can ensure efficacy beyond merely laboratory mouse models.