T1-Weighted MR imaging of liver tumor by gadolinium-encapsulated glycol chitosan nanoparticles without non-specific toxicity in normal tissues.

Abstract

Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the amine groups on the surface of Gd(iii)-CNPs could be protonated and could induce fast cellular uptake at acidic pH in tumor tissue. To assay the tumor-targeting ability of Cy5.5-labeled Gd(iii)-CNPs, near-infrared fluorescence (NIRF) imaging and MR imaging were used in a liver tumor model as well as a subcutaneous tumor model. Cy5.5-labeled Gd(iii)-CNPs generated highly intense fluorescence and T1 MR signals in tumor tissues after intravenous injection, while DOTAREM®, the commercialized control MR contrast agent, showed very low tumor-targeting efficiency on MR images. Furthermore, damaged tissues were found in the livers and kidneys of mice injected with DOTAREM®, but there were no obvious adverse effects with Gd(iii)-CNPs. Taken together, these results demonstrate the superiority of Gd(iii)-CNPs as a tumor-targeting T1 MR agent.

• Authors: Jin Hee Na, Sangmin Lee, Heebeom Koo, Hyounkoo Han, Kyung Eun Lee, Seung Jin Han, Seung Hong Choi, Hyuncheol Kim, Seulki Lee, Ick Chan Kwon, Kuiwon Choi, Kwangmeyung Kim
• Journal: Nanoscale (Nanoscale) Vol. 8 Issue 18 Pg. 9736-45 (May 05 2016) ISSN: 2040-3372 [Electronic] England
• PMID: 27113247 (Publication Type: Journal Article)

Chemical References

• Contrast Media
• Glycols
• Chitosan
• Gadolinium

Topics

• Animals
• Chitosan
• Contrast Media
• Gadolinium
• Glycols
• Liver Neoplasms (diagnostic imaging)
• Magnetic Resonance Imaging
• Mice
• Nanoparticles