Development of nanoparticle-based contrast agents for non-invasive imaging of tumor immune environment.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22497
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0403:Biomedical engineering and related fields
• Research Institution: Kyoto University
• Principal Investigator: Miura Risako 京都大学, 工学研究科, 助教 (40881694)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: 多糖 / ナノゲル / 光音響イメージング / 免疫療法

Outline of Final Research Achievements

We have developed polysaccharide nanogel-based photoacoustic imaging contrast agent targeting M2-type macrophages distributed in cold tumor. Pullulan-mannose-IR820 (PMI) was designed and synthesized by modifying pullulan, a hydrophilic polysaccharide, with IR-820, a hydrophobic near-infrared fluorescence dye, and mannose as a ligand for mannose receptors expressed on M2-type macrophages. PMI formed self-assembled nanogels by hydrophobic interaction of IR-820, and the size was 86.1 nm in diameter. PMI nanogel showed light absorption in near-infrared range, same as IR-820. The uptake of PMI nanogel by M2-type macrophages were increased compared to the nanogels without mannose, suggesting the active targeting of PMI nanogel toward mannose receptors expressed on M2-type macrophages. Finally, photoacoustic imaging of tumor-bearing mice was performed, and PMI nanogel showed higher contrast than the nanogel without mannose by improving the tumor accumulation.

Free Research Field

生体材料

Academic Significance and Societal Importance of the Research Achievements

本研究では、M2 型マクロファージと能動的に相互作用し、高い腫瘍集積性を示すナノゲル型光音響造影剤を開発した。このナノゲル型光音響造影剤は、Hot Tumor との造影能の比較を実施することで、腫瘍免疫環境の違いから Cold Tumor の非侵襲的かつ特異的な造影および診断を実現し得ると期待される。さらに、腫瘍免疫環境を正確かつ早期に画像化することにより、臨床医ががん免疫療法の治療効果を予測し、治療方法を決定する際の重要かつ有用な情報を提供可能になる。