RESUMO
Cancer gene therapy requires a safe and effective gene delivery system. Polymer- and lipid-coated magnetic nanocrystals have been used to deliver silencing RNA, but synthesizing these magnetic vectors is difficult. Here, we show that a new nanoparticle formulation can be magnetically guided to deliver and silence genes in cells and tumours in mice. This formulation, termed LipoMag, consists of an oleic acid-coated magnetic nanocrystal core and a cationic lipid shell. When compared with the commercially available PolyMag formulation, LipoMag displayed more efficient gene silencing in 9 of 13 cell lines, and better anti-tumour effects when systemically administered to mice bearing gastric tumours. By delivering an optimized sequence of a silencing RNA that targets the epidermal growth factor receptor of tumour vessels, the intended therapeutic benefit was achieved with no evident adverse immune reaction or untoward side effects.
Assuntos
DNA/administração & dosagem , Portadores de Fármacos/química , Marcação de Genes/métodos , Terapia Genética/métodos , Lipídeos/química , Nanomedicina/métodos , Nanoestruturas/uso terapêutico , Transfecção/métodos , Cristalização/métodos , DNA/química , DNA/genética , Inativação Gênica , MagnetismoRESUMO
BACKGROUND AND OBJECTIVE: We developed a new imaging system to detect sentinel nodes (SNs) using a novel fluorescent tracer, ATX-S10Na(II), and investigated its usefulness in an animal model. STUDY DESIGN/MATERIALS AND METHODS: Human gastric carcinoma cells were implanted orthotopically into nude rats. ATX-S10Na(II) was injected subserosally into the primary tumor lesion, and visualized by a fluorescence spectro-laparoscope. Presence of tumor cells in lymph nodes (LNs) was determined by RT-PCR specific for human beta-actin. RESULTS: Injection of ATX-S10Na(II) was successful in 27 tumor-bearing rats. A red fluorescence was incorporated into the left gastric and hepatic LNs in 25 and 2 rats, respectively. Of note, human beta-actin was detected in most of these LNs. Fluorescence was not detected in LNs that did not contain cancer. CONCLUSION: ATX-S10Na(II) is useful for the detection of cancer-containing SNs in an animal model of gastric carcinoma, and may serve as a novel tracer in SN navigation surgery.