Immune cell-specific delivery of beta-glucan-coated iron oxide nanoparticles for diagnosing liver metastasis by MR imaging

• Published in: Carbohydrate polymers 2012-01, Vol.87 (2), p.1159-1168
• Main Authors: Vu-Quang, Hieu, Muthiah, Muthunarayanan, Lee, Hwa Jeong, Kim, You-Kyoung, Rhee, Joon Haeng, Lee, Jae-Hyuk, Cho, Chong-Su, Choi, Yun-Jaie, Jeong, Yong Yeon, Park, In-Kyu
• Format: Article
• Language: English
• Subjects: Applied sciences; beta-glucans; Biological and medical sciences; Composites; cytotoxicity; Exact sciences and technology; Forms of application and semi-finished materials; hepatocytes; image analysis; Immune cells; immune response; Investigative techniques, diagnostic techniques (general aspects); iron oxides; light scattering; liver; Liver metastasis; lymph nodes; macrophages; magnetic resonance imaging; Medical sciences; metastasis; mice; Miscellaneous. Technology; MR imaging; nanoparticles; neoplasm cells; Polymer industry, paints, wood; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Specific targeting; Technology of polymers; transmission electron microscopy; β-Glucan
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2011.08.091

► β-Glucan coated superparamagnetic iron oxide nanoparticles (Glu-SPION) for targeting the immune cells residing in the metastatic liver. ► The in vitro uptake of Glu-SPION by peritoneal macrophages and dendritic cells confirmed with Prussian blue staining and MR phantom tube imaging. ► The in vivo accumulation of the particles in liver and lymph node was also tracked with MRI. ► Glu-SPION particles were pre-dominantly accumulated in the macrophages surrounding the metastatic region in liver. ► MR imaging clearly revealed macro- or micro-metastasized tumor regions, due to the preferential uptake of Glu-SPIONs into macrophages. Glucans are reported to elicit immune responses through activation of macrophages by a specific interaction of β-glucan with an immune cell-specific (1,3)-β-d-glucan receptor or Dectin-1 receptor. In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with β-glucan in order to target the immune cells residing in the metastatic liver as an aid for discriminating metastasized tumor regions from normal hepatic parenchymal tissue. The morphology of prepared β-glucan-coated SPIONs (Glu-SPIONs) was characterized with dynamic light scattering (DLS) and transmission electron microscopy (TEM). The cytotoxicity of Glu-SPIONs was analyzed and compared to that of dextran- and PVA-coated SPIONs. The uptake of Glu-SPIONs by peritoneal macrophages was also confirmed with Prussian blue staining and MRI phantom tube imaging. The in vivo uptake of Glu-SPIONs in liver and lymph nodes in a metastatic mouse liver model was tracked by MR imaging after the systemic injection. The Glu-SPIONs predominantly accumulated in the macrophages surrounding the metastatic regions of the liver thereby indicating the distribution of tumor cells in the liver. MR imaging of the Glu-SPIONs clearly revealed macro- or micro-metastasized tumor regions throughout the liver, due to the preferential uptake of Glu-SPIONs into macrophages, not tumor cells. The Glu-SPION-accumulating regions were further confirmed with H&E and Prussian blue stainings after tissue sectioning. Based on our study, we propose that Glu-SPIONs can be successfully applied for diagnosing hepatic metastasis.