Tumor Targeting Chitosan Nanoparticles for Dual-Modality Optical/MR Cancer Imaging

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• 作者：Taehwan Nam ; Sangjin Park ; Seung-Young Lee ; Kyeongsoon Park ; Kuiwon Choi ; In Chan Song ; Moon Hee Han ; James J. Leary ; Simseok Andrew Yuk ; Ick Chan Kwon ; Kwangmeyung Kim ; Seo Young Jeong
• 刊名：Bioconjugate Chemistry
• 出版年：2010
• 出版时间：April 21, 2010
• 年：2010
• 卷：21
• 期：4
• 页码：578-582
• 全文大小：261K
• 年卷期：v.21,no.4(April 21, 2010)
• ISSN：1520-4812

文摘

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 5β-cholanic acid (CA), resulting in amphiphilic glycol chitosan-5β-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 GdCl₃ 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.