Stimuli-responsive Graphene Nanoplatforms Co-delivering Self-amplifying RNA, circRNA, and cGAMP for Cancer Immunotherapy: A Narrative Review.

INTRODUCTION

Cancer immunotherapy has emerged as a transformative therapeutic strategy; however, its efficacy remains limited by tumor heterogeneity, immune suppression, and inefficient delivery of nucleic acid therapeutics. Graphene-based nanomaterials have attracted considerable attention as multifunctional carriers because of their high surface area, tunable surface chemistry, and stimuli-responsive properties.

METHODS

This narrative review critically summarizes recent advances in stimuli-responsive graphene nanoplatforms for the co-delivery of self-amplifying RNA (saRNA), circular RNA (circRNA), and cGAMP. A conceptual multifunctional graphene-based delivery framework is proposed to guide future experimental research in cancer immunotherapy. Particular emphasis is placed on graphene functionalization strategies, RNA conjugation approaches, tumor-responsive release mechanisms, and synergistic immune activation pathways.

RESULTS

Graphene nanoplatforms demonstrate significant potential to protect nucleic acid therapeutics from degradation while enabling controlled release in response to pH, redox, enzymatic, and near-infrared stimuli. The integration of saRNA, circRNA, and cGAMP provides complementary therapeutic benefits, including prolonged antigen expression, enhanced molecular stability, and potent activation of the STING pathway. This combination promotes coordinated activation of innate and adaptive immunity, resulting in improved dendritic cell maturation, T-cell priming, and antitumor immune responses.

DISCUSSION: The multifunctional nature of graphene-based nanocarriers offers opportunities for simultaneous delivery of multiple immunotherapeutic agents while reducing systemic toxicity. Nevertheless, challenges related to biosafety, biodegradability, large-scale manufacturing, and regulatory approval remain barriers to clinical translation.

CONCLUSION

Stimuli-responsive graphene nanoplatforms co-delivering saRNA, circRNA, and cGAMP represent a promising next-generation strategy for precision cancer immunotherapy. Continued advances in graphene engineering and translational nanomedicine may facilitate their future clinical application.