RRC ID 69459
Author Kono Y, Kawakami S, Higuchi Y, Maruyama K, Yamashita F, Hashida M.
Title Tumour-associated macrophages targeted transfection with NF-κB decoy/mannose-modified bubble lipoplexes inhibits tumour growth in tumour-bearing mice.
Journal J Drug Target
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.
Volume 22(5)
Pages 439-49
Published 2014-6-1
DOI 10.3109/1061186X.2014.880443
PMID 24579693
MeSH Animals Colonic Neoplasms / genetics Colonic Neoplasms / immunology Colonic Neoplasms / pathology Colonic Neoplasms / therapy* Drug Carriers / chemistry* Female Gene Transfer Techniques Liposomes Macrophages / metabolism* Mannose / chemistry* Mice, Inbred BALB C Neoplasm Transplantation Oligodeoxyribonucleotides / genetics* Polyethylene Glycols / chemistry Real-Time Polymerase Chain Reaction Survival Analysis Transfection Ultrasonics
IF 3.38
Human and Animal Cells Colon-26(RCB2657)