TY - JOUR
T1 - Liver-targeting MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan
AU - Xu, Li
AU - Ren, Zhanying
AU - Li, Guolin
AU - Xu, Danni
AU - Miao, Jiaqian
AU - Ju, Jingxuan
AU - Mo, Xuan
AU - Wang, Xianghui
AU - Deng, Hongping
AU - Xu, Min
N1 - Publisher Copyright:
Copyright © 2023 Xu, Ren, Li, Xu, Miao, Ju, Mo, Wang, Deng and Xu.
PY - 2023
Y1 - 2023
N2 - Commercial gadolinium (Gd)-based contrast agents (GBCAs) play important role in clinical diagnostic of hepatocellular carcinoma, but their diagnostic efficacy remained improved. As small molecules, the imaging contrast and window of GBCAs is limited by low liver targeting and retention. Herein, we developed a liver-targeting gadolinium (Ⅲ) chelated macromolecular MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan, namely, CS-Ga-(Gd-DTPA)n, to improve hepatocyte uptake and liver retention. Compared to Gd-DTPA and non-specific macromolecular agent CS-(Gd-DTPA)n, CS-Ga-(Gd-DTPA)n showed higher hepatocyte uptake, excellent cell and blood biocompatibility in vitro. Furthermore, CS-Ga-(Gd-DTPA)n also exhibited higher relaxivity in vitro, prolonged retention and better T1-weighted signal enhancement in liver. At 10 days post-injection of CS-Ga-(Gd-DTPA)n at a dose of 0.03 mM Gd/Kg, Gd had a little accumulation in liver with no liver function damage. The good performance of CS-Ga-(Gd-DTPA)n gives great confidence in developing liver-specifc MRI contrast agents for clinical translation.
AB - Commercial gadolinium (Gd)-based contrast agents (GBCAs) play important role in clinical diagnostic of hepatocellular carcinoma, but their diagnostic efficacy remained improved. As small molecules, the imaging contrast and window of GBCAs is limited by low liver targeting and retention. Herein, we developed a liver-targeting gadolinium (Ⅲ) chelated macromolecular MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan, namely, CS-Ga-(Gd-DTPA)n, to improve hepatocyte uptake and liver retention. Compared to Gd-DTPA and non-specific macromolecular agent CS-(Gd-DTPA)n, CS-Ga-(Gd-DTPA)n showed higher hepatocyte uptake, excellent cell and blood biocompatibility in vitro. Furthermore, CS-Ga-(Gd-DTPA)n also exhibited higher relaxivity in vitro, prolonged retention and better T1-weighted signal enhancement in liver. At 10 days post-injection of CS-Ga-(Gd-DTPA)n at a dose of 0.03 mM Gd/Kg, Gd had a little accumulation in liver with no liver function damage. The good performance of CS-Ga-(Gd-DTPA)n gives great confidence in developing liver-specifc MRI contrast agents for clinical translation.
KW - biocompatibility
KW - gadolinium (Gd)-based MRI contrast agents
KW - galactose functionized o-carboxymethyl chitosan
KW - imaging contrast
KW - liver-targeting
UR - https://www.scopus.com/pages/publications/85161000783
U2 - 10.3389/fbioe.2023.1134665
DO - 10.3389/fbioe.2023.1134665
M3 - 文章
AN - SCOPUS:85161000783
SN - 2296-4185
VL - 11
JO - Frontiers in Bioengineering and Biotechnology
JF - Frontiers in Bioengineering and Biotechnology
M1 - 1134665
ER -