材料的手性直接影响其在生理条件下的运输和生物效应。然而，手性材料对细胞代谢重编程的影响仍未完全阐明。在这项研究中，我们通过光驱动颗粒生长方法合成了手性金颗粒，并证明与 l-Au 颗粒相比，d-Au 颗粒表现出更优异的巨噬细胞激活能力。 d-Au 刺激后诱导炎症肌酸-磷酸肌酸分流。这种分流是由肌酸激酶肌肉型（CKM）表达上调促进的，也导致细胞质中肌酸水平的降低。 CKM 的药理学抑制和基因消除进一步抑制促炎细胞因子的分泌，而不影响线粒体呼吸。此外，d-Au 诱导的巨噬细胞激活是通过激活 NF-κB 和 NLRP3 炎性体途径介导的。抑制 CKM 表达不仅减少 CXCL2 的分泌，还通过抑制 NLRP3 炎性体途径减弱 IL-1β。我们对手性材料对巨噬细胞激活的代谢重编程机制的研究对于基于手性的抗癌疗法的应用至关重要。

The chirality of materials directly influences their transport and biological effects in physiological conditions. However, the impact of chiral materials on cellular metabolic reprogramming remains incompletely elucidated. In this study, we have synthesized chiral gold particles through a light-driven particle growth approach and demonstrated that d-Au particles exhibited superior macrophage activation ability compared to l-Au particles. An inflammatory creatine-phosphocreatine shunt was induced following d-Au stimulation. This shunt, facilitated by the upregulated expression of creatine kinase muscle-type (CKM), also resulted in a reduction in cytosolic levels of creatine. Pharmacological inhibition and genetic ablation of CKM further suppressed the secretion of pro-inflammatory cytokines, without compromising mitochondrial respiration. Moreover, the activation of macrophages induced by d-Au was mediated through the activation of the NF-κB and NLRP3 inflammasome pathways. Inhibition of CKM expression not only decreased the secretion of CXCL2 but also attenuated IL-1β by suppressing the NLRP3 inflammasome pathways. Our investigation into the metabolic reprogramming mechanism of chiral materials on macrophage activation is pivotal for the application of chiral-based anticancer therapies.