The Development of Chiral Nanoparticles to Target NK Cells and CD8⁺ T Cells for Cancer Immunotherapy

Abstract The chirality of nanomaterials (nanoparticles, NPs) can influence their interaction with cells and biological systems. However, how chirality can exert impact on the immune response has yet to be investigated. Here, the immunological effect of chiral nanomaterials is investigated as a therapeutic and preventive option against tumors. Compared with achiral nanoparticles, chiral NPs with a g‐factor of 0.44 are shown to enhance both innate and acquired immunity against tumor growth. It is also found that chiral NPs enhance the activation of CD8⁺ T and natural killer cells (CD69⁺ NK cells) by stimulating dendritic cells (DCs). Importantly, L‐type NPs induce a 1.65‐fold higher proportion of CD8⁺ T and CD69⁺ NK cells than D‐type NPs. Next, the therapeutic and preventative effects of chiral NPs against tumors in a EG7.OVA tumor model are investigated. It is found that L‐type NPs have a significant greater ability to induce apoptosis in tumor cells and prolong the survival time of model mice than D‐type NPs. Mice treated with L‐type NPs induce the activation of 84.98 ± 6.63% CD8⁺ T cells and 33.62 ± 3.41% of NK cells in tumor tissues; these are 1.62‐fold and 1.39‐fold higher than that seen in the mice treated with D‐type NPs. Mechanistic studies reveal that chiral NPs exert mechanical force on bone‐marrow‐derived dendritic cells (BMDCs) and stimulate the expression of cytokines to induce cytotoxic activity in NK cells. Synergistically, the CD8⁺ T cells are stimulated to eliminate tumor cells via antigen cross presentation. The force of interaction between L‐type NPs and cells is higher than that for D‐NPs, thus further promoting the activation of NK cells and CD8⁺ T cells and their infiltration into tumor tissue. These findings open up a new avenue for chiral nanomaterials to act as immunoadjuvants for the prevention and treatment of cancer.