Tumour-associated macrophages targeted transfection with NF-kappa B decoy/mannose-modified bubble lipoplexes inhibits tumour growth in tumour-bearing mice

摘要

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-kappa B is a key regulator of macrophage polarization, we developed an in vivo TAM-targeting delivery system that combines mannose-modified bubble liposomes/ NF-kappa B decoy complexes (Man-PEG bubble lipoplexes) and ultrasound (US) exposure. We investigated the effects of NF-kappa B decoy transfection on TAM phenotype in solid tumourbearing mice. Post-transfection tumour growth and survival rates were also recorded. Th2 cytokine (IL-10) level in TAM was significantly lower by NF-kappa B decoy transfection using Man-PEG bubble lipoplexes and US exposure, while Th1 cytokine levels (IL-1 beta, TNF-alpha 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-kappa B decoy transfection. Importantly, TAM-targeted NF-kappa B decoy transfection inhibited tumour growth and prolonged survival rates in mice. Therefore, TAM-targeted NF-kappa B 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.