Tumour-associated macrophages targeted transfection with NF-κB decoy/mannose-modified bubble lipoplexes inhibits tumour growth in tumour-bearing mice.
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| Abstract |
Tumour-associated macrophages (TAM) exhibit an M2 phenotype that promotes tumour progression, and conversion of M2 TAM toward a tumouricidal M1 phenotype is a promising anti-cancer therapy. As NF-κB is a key regulator of macrophage polarization, we developed an in vivo TAM-targeting delivery system that combines mannose-modified bubble liposomes/NF-κB decoy complexes (Man-PEG bubble lipoplexes) and ultrasound (US) exposure. We investigated the effects of NF-κB decoy transfection on TAM phenotype in solid tumour-bearing mice. Post-transfection tumour growth and survival rates were also recorded. Th2 cytokine (IL-10) level in TAM was significantly lower by NF-κB decoy transfection using Man-PEG bubble lipoplexes and US exposure, while Th1 cytokine levels (IL-1β, TNF-α and IL-6) were significantly higher when compared with controls. In addition, mRNA levels of vascular endothelial growth factor, matrix metalloproteinase-9 and arginase were significantly lower in TAM post-NF-κB decoy transfection. Importantly, TAM-targeted NF-κB decoy transfection inhibited tumour growth and prolonged survival rates in mice. Therefore, TAM-targeted NF-κB decoy transfection using Man-PEG bubble lipoplexes and US exposure may be an effective approach for anti-cancer therapy based on TAM phenotypic conversion from M2 toward M1.
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| Authors | Yusuke Kono, Shigeru Kawakami, Yuriko Higuchi, Kazuo Maruyama, Fumiyoshi Yamashita, Mitsuru Hashida |
| Journal | Journal of drug targeting (J Drug Target) Vol. 22 Issue 5 Pg. 439-49 (Jun 2014) ISSN: 1029-2330 [Electronic] England |
| PMID | 24579693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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