RESUMO
High accumulation and selective delivery of boron into tumor tissues are the most important requirements to achieve efficient neutron capture therapy of cancers. We focused on liposomal boron delivery system in order to achieve a large amount of boron delivery to tumor. We synthesized the double-tailed boron cluster lipid 4c according to our reported procedure with modification. Size distribution of liposomes prepared from the boron cluster lipid 4c, DMPC, PEG-DSPE, and cholesterol was determined as 100 nm in diameter by an electrophoretic light scattering spectrophotometer. A high level of (10)B concentration (22 ppm) was observed in tumor tissue at 24 h after the administration of boron liposomes.
Assuntos
Compostos de Boro/administração & dosagem , Terapia por Captura de Nêutron de Boro/métodos , Nanocápsulas/uso terapêutico , Radiossensibilizantes/administração & dosagem , Animais , Compostos de Boro/síntese química , Compostos de Boro/química , Compostos de Boro/uso terapêutico , Isótopos/administração & dosagem , Isótopos/uso terapêutico , Lipossomos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/radioterapia , Tamanho da Partícula , Radiossensibilizantes/síntese química , Radiossensibilizantes/química , Radiossensibilizantes/uso terapêutico , Distribuição TecidualRESUMO
The potential for gene therapy to be an effective treatment for cystic fibrosis has been hampered by the limited gene transfer efficiency of current vectors. We have shown that recombinant Sendai virus (SeV) is highly efficient in mediating gene transfer to differentiated airway epithelial cells, because of its capacity to overcome the intra- and extracellular barriers known to limit gene delivery. Here, we have identified a novel method to allow the cystic fibrosis transmembrane conductance regulator (CFTR) cDNA sequence to be inserted within SeV (SeV-CFTR). Following in vitro transduction with SeV-CFTR, a chloride-selective current was observed using whole-cell and single-channel patch-clamp techniques. SeV-CFTR administration to the nasal epithelium of cystic fibrosis (CF) mice (Cftr(G551D) and Cftr(tm1Unc)TgN(FABPCFTR)#Jaw mice) led to partial correction of the CF chloride transport defect. In addition, when compared to a SeV control vector, a higher degree of inflammation and epithelial damage was found in the nasal epithelium of mice treated with SeV-CFTR. Second-generation transmission-incompetent F-deleted SeV-CFTR led to similar correction of the CF chloride transport defect in vivo as first-generation transmission-competent vectors. Further modifications to the vector or the host may make it easier to translate these studies into clinical trials of cystic fibrosis.