〔Abstract〕 Objective Cas9-RNP biomimetic nanoparticles cas9-RNP@MMs were prepared by encapsulating the Cas9 Ribonucleoprotein complex(RNP) using mouse macrophage membranes, with the aim of utilizing this biomimetic nanoparticle to deliver the Cas9-RNP complex for gene editing, and further study the endocytosis of Cas9-RNP@MMs and its gene editing effect in mouse macrophage RAW264.7in vitro, providing evidence for the development of low-toxicity biomimetic nanoparticle carriers that inhibitNLRP3 therapeutic targets. Methods The purified mouse macrophage membrane was mixed with the prepared cas9-RNP mixture, and after ultrasound, the CAS9-RNP@MMS was obtained by liposome extrusion instrument; The particle size of Cas9-RNP@MMs was measured by nanoparticle tracking analysis, and the particle morphology of Cas9-RNP@MMs was observed under transmission electron microscope. Laser confocal Fluorescence microscope imaging was used to analyze the endocytosis Cas9-RNP@MMs.The Biocompatibility of Cas9-RNP@MMs was measured by MTT assay. The expression ofNLRP3 was detected by qPCR and Western blot to verify the knockdown effect of Cas9-RNP@MMs onNLRP3 gene. Results The average particle diameter of Cas9-RNP@MMs prepared from macrophages was about 216 nm. Under laser confocal fluorescence microscope, the Cas9-RNP@MMs could be successfully endocysed by Raw246.7 cell. MTT assay indicated that the Cas9-RNP@MMs-treated mouse macrophage RAW246. 7 had good biocompatibility. qPCR and Western blot showed that twoNLRP3-specific guide RNA were mediated by Cas9-RNP@MMs, with good effect of knockdownNLRP3 gene expression. Conclusion Nano-scale vesicles Cas9-RNP@MMs loaded with Cas9-RNP complexes were successfully prepared by biomimetic nanoparticles. Cas9-RNP@MMs have good biocompatibility and can be efficiently endocytosed by RAW246.7 cells. Cas9-RNP@MMs containingNLRP3-specific sgRNA can specifically knock downNLRP3 gene expression.