Wang Weiwei, Zhao Jing, Hao Changlong, Hu Shudong, Chen Chen, Cao Yi, Xu Zhengyu, Guo Jun, Xu Liguang, Sun Maozhong, Xu Chuanlai, Kuang Hua
International Joint Research Laboratory for Biointerface and Biodetection, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
Department of Radiology, Affiliated Hospital, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
Adv Mater. 2022 Apr;34(16):e2109354. doi: 10.1002/adma.202109354. Epub 2022 Mar 10.
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.
纳米材料（纳米颗粒，NPs）的手性能够影响它们与细胞及生物系统的相互作用。然而，手性如何对免疫反应产生影响还有待研究。在此，研究了手性纳米材料的免疫效应，将其作为一种针对肿瘤的治疗和预防手段。与非手性纳米颗粒相比，g因子为0.44的手性NPs显示出能增强针对肿瘤生长的固有免疫和获得性免疫。还发现手性NPs通过刺激树突状细胞（DCs）增强CD8 T细胞和自然杀伤细胞（CD69 NK细胞）的活化。重要的是，L型NPs诱导产生的CD8 T细胞和CD69 NK细胞比例比D型NPs高1.65倍。接下来，研究了手性NPs在EG7.OVA肿瘤模型中对肿瘤的治疗和预防作用。发现L型NPs比D型NPs具有显著更强的诱导肿瘤细胞凋亡及延长模型小鼠存活时间的能力。用L型NPs处理的小鼠在肿瘤组织中诱导84.98±6.63%的CD8 T细胞和33.62±3.41%的NK细胞活化；这些比例分别比用D型NPs处理的小鼠高1.62倍和1.39倍。机制研究表明，手性NPs对骨髓来源的树突状细胞（BMDCs）施加机械力并刺激细胞因子表达以诱导NK细胞的细胞毒活性。协同地，CD8 T细胞被刺激通过抗原交叉呈递消除肿瘤细胞。L型NPs与细胞之间的相互作用力高于D型NPs，从而进一步促进NK细胞和CD8 T细胞的活化及其向肿瘤组织的浸润。这些发现为手性纳米材料作为癌症预防和治疗的免疫佐剂开辟了一条新途径。
