Tumor targeting chitosan nanoparticles for dual-modality optical/MR cancer imaging.
We report tumor targeting nanoparticles for optical/MR dual imaging based on self-assembled glycol chitosan to be a potential multimodal imaging probe. To develop an optical/MR dual imaging probe, biocompatible and water-soluble glycol chitosan (M(w) = 50 kDa) were chemically modified with 5beta-cholanic acid (CA), resulting in amphiphilic glycol chitosan-5beta-cholanic acid conjugates (GC-CA). For optical imaging near-infrared fluorescence (NIRF) dye, Cy5.5, was conjugated to GC-CA resulting in Cy5-labeled GC-CA conjugates (Cy5.5-GC-CA). Moreover, in order to chelate gadolinium (Gd(III)) in the Cy5.5-GC-CA conjugates, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was directly conjugated in Cy5.5-GC-CA. Finally, the excess GdCl(3) was added to DOTA modified Cy5.5-GC-CA conjugates in distilled water (pH 5.5). The freshly prepared Gd(III) encapsulated Cy5.5-GC-CA conjugates were spontaneously self-assembled into stable Cy5.5 labeled and Gd(III) encapsulated chitosan nanoparticles (Cy5.5-CNP-Gd(III)). The Cy5.5-CNP-Gd(III) was spherical in shape and approximately 350 nm in size. From the cellular experiment, it was demonstrated that Cy5.5-CNP-Gd(III) were efficiently taken up and distributed in cytoplasm (NIRF filter; red). When the Cy5.5-GC-Gd(III) were systemically administrated into the tail vein of tumor-bearing mice, large amounts of nanoparticles were successfully localized within the tumor, which was confirmed by noninvasive near-infrared fluorescence and MR imaging system simultaneously. These results revealed that the dual-modal imaging probe of Cy5.5-CNP-Gd(III) has the potential to be used as an optical/MR dual imaging agent for cancer treatment.
Nam
Taehwan
T
Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea.
Park
Sangjin
S
Lee
Seung-Young
SY
Park
Kyeongsoon
K
Choi
Kuiwon
K
Song
In Chan
IC
Han
Moon Hee
MH
Leary
James J
JJ
Yuk
Simseok Andrew
SA
Kwon
Ick Chan
IC
Kim
Kwangmeyung
K
Jeong
Seo Young
SY
D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry; D002793:Cholic Acids / Q000737:chemistry; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000175:diagnosis*; D019265:Spectroscopy, Near-Infrared
D002793:Cholic Acids; D005456:Fluorescent Dyes; C118638:glycol-chitosan; D048271:Chitosan; D005682:Gadolinium; C007036:cholanic acid