T1-Weighted MR imaging of liver tumor by gadolinium-encapsulated glycol chitosan nanoparticles without non-specific toxicity in normal tissues.
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.
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea. kim@kist.re.kr and The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N. Caroline Street, Baltimore, MD 21287, USA and The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.
Jin Hee
JH
Na
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea. kim@kist.re.kr and The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N. Caroline Street, Baltimore, MD 21287, USA and The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.
Sangmin
S
Lee
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea. kim@kist.re.kr.
Heebeom
H
Koo
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea. kim@kist.re.kr and Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, Republic of Korea.
Hyounkoo
H
Han
Advanced Analysis Center, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.
Kyung Eun
KE
Lee
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea. kim@kist.re.kr.
Seung Jin
SJ
Han
Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea.
Seung Hong
SH
Choi
Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, Republic of Korea.
Hyuncheol
H
Kim
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N. Caroline Street, Baltimore, MD 21287, USA and The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.
Seulki
S
Lee
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea. kim@kist.re.kr and KU-KIST School, Korea University, 1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
Ick Chan
IC
Kwon
Korea Institute of Science and Technology Europe (KIST-Europe), Forschungsgesellschaft mbH, Campus E7.1, 66123 Saarbrücken, Germany.
Kuiwon
K
Choi
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea. kim@kist.re.kr.
Kwangmeyung
K
Kim
D000818:Animals; D048271:Chitosan; D003287:Contrast Media; D005682:Gadolinium; D006018:Glycols; D008113:Liver Neoplasms / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D051379:Mice; D053758:Nanoparticles
D003287:Contrast Media; D006018:Glycols; D048271:Chitosan; D005682:Gadolinium