Unified therapeutic-prophylactic nucleobase-lipid nanovaccine with STING pathway agonist (2'3'-cGAMP) to prevent tumor growth recurrence and metastasis.

The development of cancer nanovaccines capable of simultaneously treating tumors and effectively preventing tumor recurrence and metastasis continues to pose significant challenges. In this study, we engineered a nucleobase liposome vaccine that amalgamated anti-tumor, anti-metastatic, and anti-recurrence properties. The nanovaccine 2'3'-cGAMP@DTL was formulated with a nucleobase-lipid loaded immune adjuvant 2'3'-cGAMP. On the one hand, 2'3'-cGAMP@DTL activated innate immunity by stimulating the stimulator of interferon genes (STING) pathway, thereby inhibited tumor proliferation. On the other hand, 2'3'-cGAMP@DTL enhanced STING pathway activation to promote the proliferation of CD4+ and CD8+ T cells in tumor metastasis and postoperative models, 2'3'-cGAMP@DTL inhibited the growth of both primary and postoperative tumors. In conclusion, nanovaccine 2'3'-cGAMP@DTL demonstrated significant efficacy in suppressing tumor growth and reducing postsurgical tumor recurrence and metastasis, thereby offering straightforward and effective therapeutic strategies for tumors patients.