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Patients with malignant ascites ( MA s) display several symptoms, such as dyspnea, nausea, pain, and abdominal tenderness, resulting in a significant reduction in their quality of life. Tumor‐associated macrophages ( TAM s) play a crucial role in  MA  progression. Because  TAM s have a tumor‐promoting M2 phenotype, conversion of the M2 phenotypic function of  TAM s would be promising for  MA  treatment. Nuclear factor‐κB (NF‐κB) is a master regulator of macrophage polarization. Here, we developed targeted transfer of a  NF ‐κB decoy into  TAM s by ultrasound ( US )‐responsive, mannose‐modified liposome/ NF ‐κB decoy complexes (Man‐ PEG  bubble lipoplexes) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. In addition, we investigated the effects of  NF ‐κB decoy transfection into  TAM s on  MA  progression and mouse survival rates. Intraperitoneal injection of Man‐ PEG  bubble lipoplexes and  US  exposure transferred the  NF ‐κB decoy into  TAM s effectively. When the  NF ‐κB decoy was delivered into  TAM s by this method in the mouse peritoneal dissemination model, m RNA  expression of the Th2 cytokine interleukin ( IL )‐10 in  TAM s was decreased significantly. In contrast, m RNA  levels of Th1 cytokines ( IL ‐12, tumor necrosis factor‐α, and  IL ‐6) were increased significantly. Moreover, the expression level of vascular endothelial growth factor in ascites was suppressed significantly, and peritoneal angiogenesis showed a reduction. Furthermore,  NF ‐κB decoy transfer into  TAM s significantly decreased the ascitic volume and number of Ehrlich ascites carcinoma cells in ascites, and prolonged mouse survival. In conclusion, we transferred a  NF ‐κB decoy efficiently by Man‐ PEG  bubble lipoplexes with  US  exposure into  TAM s, which may be a novel approach for  MA  treatment.

Antitumor effect of nuclear factor‐κB decoy transfer by mannose‐modified bubble lipoplex into macrophages in mouse malignant ascites