Split bullets loaded nanoparticles for amplified immunotherapy

Dendritic cells (DCs) play central role in adaptive antitumor immunity, while their function is often hampered by low immunogenicity of tumor tissues and surrounding hostile microenvironment. Herein, a split bullets loaded nanoplatform that can bidirectionally injure mitochondria (MT) and endoplasmic reticulum (ER) of tumor cells is developed. After cellular uptake, the released split bullets separately target to different subcellular destinations and exert distinct effects on DCs: (1) MT-targeted bullet recruits peripheral DCs into tumor sites, due to its capability to trigger adenosine triphosphate release from tumor cells; (2) ER-targeted bullet activates tumorinfiltrating DCs, which is attributed to its ability to evoke calreticulin exposure on tumor cells. These effects collectively improve the tropism and reactivity of DCs to tumor-specific antigen in a two-pronged way. As a result of enhanced function of DCs in antigen capture, treatment of the split bullets loaded nanoplatform ignites robust immune response to suppress primary melanoma, and establishes systemic immune memory against post-surgical tumor recurrence. Overall, this nanoplatform offers a generalizable approach to boost DCs and augment immunotherapy.

Automated summary

A split bullets loaded nanoplatform is developed to enhance the function of dendritic cells (DCs) in adaptive antitumor immunity by bidirectionally damaging the mitochondria and endoplasmic reticulum of tumor cells.