title: SPIO-PICsome: development of a highly sensitive and stealth-capable MRI nano-agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles (PICsomes).
abstract: Size controllable polyion complex vesicles (PICsomes), composed of biocompatible poly(ethylene glycol) (PEG) and poly(amino acid)s, have an extremely prolonged lifetime in the bloodstream that enables them to accumulate effectively in tumors via the enhanced permeability and retention (EPR) effect. The purpose of this study was to use PICsomes to synthesize a highly sensitive MRI contrast agent for more precise tumor detection. We synthesized SPIO-Cy5-PICsomes (superparamagnetic iron oxide nanoparticle-loaded Cy5-cross-linked Nano-PICsomes) and characterized them using dynamic light scattering and transmission electron microscopy in vitro and evaluated their ability to detect subcutaneously grafted tumors in vivo with MRI. The transverse relaxivity (r2) of the SPIO-Cy5-PICsomes (r2=663±28mM(-1)s(-1)) was 2.54 times higher than that of bare clinically-used SPIO. In in vivo MRI experiments on mice subcutaneously grafted with colon-26 tumor cells, the tumor signal was significantly altered at 3h after SPIO-Cy5-PICsome administration and persisted for at least 24h. Small and early-stage in vivo tumors (3days after grafting, approximately 4mm(3)) were also clearly detected with MRI. SPIO-loaded PICsomes are sensitive MRI contrast agents that can act as a powerful nanocarrier to detect small tumors for early diagnosis.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba-city 263-8555, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kokuryo
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Anraku
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kishimura
authors.forename: Sayaka
authors.initials: S
authors.lastname: Tanaka
authors.forename: Mitsunobu R
authors.initials: MR
authors.lastname: Kano
authors.forename: Jeff
authors.initials: J
authors.lastname: Kershaw
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D002232:Carbocyanines / Q000138:chemical synthesis / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000596:Amino Acids; D002232:Carbocyanines; D003287:Contrast Media; D058185:Magnetite Nanoparticles; C085321:cyanine dye 5; D011092:Polyethylene Glycols