title: Tumour-associated macrophages targeted transfection with NF-κB decoy/mannose-modified bubble lipoplexes inhibits tumour growth in tumour-bearing mice.
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.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto , Japan .
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kono
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D018014:Gene Transfer Techniques; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism*; D008358:Mannose / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000235:genetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis; D014162:Transfection; D014465:Ultrasonics
chemical_list: D004337:Drug Carriers; D008081:Liposomes; C468119:NF-kappaB decoy; D009838:Oligodeoxyribonucleotides; D011092:Polyethylene Glycols; D008358:Mannose
keywords: Cancer therapy; oligonucleotides; phenotype; sonoporation