A novel magnetic crystal-lipid nanostructure for magnetically guided in vivo gene delivery.
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.
Namiki
Yoshihisa
Y
Institute of Clinical Medicine and Research, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, Japan. cancer_gene_therapy@ybb.ne.jp
Namiki
Tamami
T
Yoshida
Hiroshi
H
Ishii
Yukiko
Y
Tsubota
Akihito
A
Koido
Shigeo
S
Nariai
Kouichi
K
Mitsunaga
Makoto
M
Yanagisawa
Satoru
S
Kashiwagi
Hideyuki
H
Mabashi
Yasuo
Y
Yumoto
Yoko
Y
Hoshina
Sadayori
S
Fujise
Kiyotaka
K
Tada
Norio
N
D003460:Crystallization / Q000379:methods; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry*; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D008055:Lipids / Q000737:chemistry*; D008280:Magnetics; D050997:Nanomedicine / Q000379:methods*; D049329:Nanostructures / Q000627:therapeutic use*; D014162:Transfection / Q000379:methods*
D004337:Drug Carriers; D008055:Lipids; D004247:DNA