Cocktail nano-adjuvant enhanced cancer immunotherapy based on NIR-II-triggered in-situtumor vaccination

Second near-infrared (NIR-II) light triggered in-situtumor vaccination (ISTV) represents one of the most promising strategies in boosting the whole-body antitumor immunity. While most of previously developed nano-adjuvants for NIR-II-triggered ISTV are “all-in-one” formulations, which may indiscriminately damage both the tumor cells and the immune cells, limiting the overall effect of immune response. To overcome this obstacle, we designed a “cocktail” nano-adjuvant by physically mixing hyaluronidases (HAase)-decorated gold nanostars (HA) for NIR-II light triggered in situproduction of tumor-associated antigens and CpG functionalized gold nanospheres (CA) for immune cells activation. Compared to “all-in-one” formulation, the “cocktail” nano-adjuvants displayed a significantly stronger immune response on NIR-II light induced dendritic cells (DCs) mutation and T cells differentiation, greater effect on tumor-growth inhibition, and higher efficacy in inhibition of pulmonary metastases. What is more, increasing the molar ratio of HA to CA led to an enhanced anticancer immune responses. This study highlight the nano-adjuvant formulation effects on the treatment of tumors with multiple targets.