Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

Abstract

Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

• Authors: Jihong Sun, Shizheng Zhang, Shaojie Jiang, Weixian Bai, Fei Liu, Hong Yuan, Jiansong Ji, Jingfeng Luo, Guocan Han, Lumin Chen, Yin Jin, Peng Hu, Lei Yu, Xiaoming Yang
• Journal: Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 12 Issue 9 Pg. 1709-23 (Sep 2016) ISSN: 1550-7033 [Print] United States
• PMID: 29345451 (Publication Type: Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Journal Article)

Chemical References

• Contrast Media
• Gadolinium DTPA

Topics

• Animals
• Cell Line, Tumor
• Colorectal Neoplasms (diagnostic imaging)
• Contrast Media (chemistry, pharmacokinetics)
• Early Detection of Cancer (methods)
• Gadolinium DTPA (chemistry, pharmacokinetics)
• HT29 Cells
• Humans
• Magnetic Resonance Imaging (methods)
• Mice