@article{oai:nagasaki-u.repo.nii.ac.jp:00005746,
 author = {Kono, Yusuke and Kawakami, Shigeru and Higuchi, Yuriko and Maruyama, Kazuo and Yamashita, Fumiyoshi and Hashida, Mitsuru},
 issue = {8},
 journal = {Cancer Science},
 month = {Aug},
 note = {Patients with malignant ascites (MAs) display several symptoms, such as dyspnea, nausea, pain, and abdominal tenderness, resulting in a significant reduction in their quality of life. Tumor-associated macrophages (TAMs) play a crucial role in MA progression. Because TAMs have a tumor-promoting M2 phenotype, conversion of the M2 phenotypic function of TAMs 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 TAMs 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 TAMs on MA progression and mouse survival rates. Intraperitoneal injection of Man-PEG bubble lipoplexes and US exposure transferred the NF-κB decoy into TAMs effectively. When the NF-κB decoy was delivered into TAMs by this method in the mouse peritoneal dissemination model, mRNA expression of the Th2 cytokine interleukin (IL)-10 in TAMs was decreased significantly. In contrast, mRNA 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 TAMs 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 TAMs, which may be a novel approach for MA treatment. We demonstrated that the combinatorial use of mannose-modified bubble lipoplexes with ultrasound exposure achieved the efficient delivery of NF-κB decoy oligonucleotides into tumor-associated macrophages (TAM) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. Using this method, NF-κB decoy transfer into TAM inhibited the malignant ascites progression significantly that may be the phenotypic conversion of TAM from M2 toward M1., Cancer Science, 105(8), pp.1049-1055; 2014},
 pages = {1049--1055},
 title = {Antitumor effect of nuclear factor-κB decoy transfer by mannose-modified bubble lipoplex into macrophages in mouse malignant ascites},
 volume = {105},
 year = {2014}
}