Open AccessAntitumor effect of nuclear factor‐κB decoy transfer by mannose‐modified bubble lipoplex into macrophages in mouse malignant ascites
Author(s) -
Kono Yusuke,
Kawakami Shigeru,
Higuchi Yuriko,
Maruyama Kazuo,
Yamashita Fumiyoshi,
Hashida Mitsuru
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12452
Subject(s) - decoy , ascites , cancer research , medicine , peritoneal cavity , tumor necrosis factor alpha , inflammation , ehrlich ascites carcinoma , intraperitoneal injection , pathology , receptor , tumor cells , anatomy
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.