Development of gene and nucleic acid medicines for lung cancer based on the multifunctional pulmonary nanoparticles

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Nagasaki University
• Principal Investigator: Kodama Yukinobu 長崎大学, 病院(医学系), 准教授 (50448510)
• Co-Investigator(Kenkyū-buntansha): 川上 茂 長崎大学, 医歯薬学総合研究科(薬学系), 教授 (20322307)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 遺伝子デリバリー / 経肺投与 / ナノ微粒子 / 遺伝子・核酸医薬

Outline of Final Research Achievements

In this study, we developed gene and nucleic acid medicines for lung cancer based on multifunctional pulmonary nanoparticles. We constructed nanoparticles which are efficiently taken up by alveolar macrophages by optimizing the mixing ratio of pDNA, dendrigraft poly-L-lysine, and γ-polyglutamic acid. Nano particles showed high gene expression in areas rich in alveolar macrophages and alveolar epithelial type II cells after pulmonary administration. High gene expression was selectively observed in areas rich in alveolar macrophages in mice after pulmonary administration of nanoparticles. As a result of applying it to a melanoma DNA vaccine, it stimulated immunity and suppressed lung metastasis. In addition, lung metastasis of melanoma was significantly suppressed after pulmonary administration of nanoparticles containing siRNA against proteins involved in tumor growth or metastasis. It was shown that these nanoparticles could contribute to a wide range of lung cancer drugs.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

本研究により、肺に選択的に送達できる経肺投与型のナノ微粒子の調製に成功した。このナノ微粒子は肺胞マクロファージや肺胞上皮Ⅱ型細胞に良好に取り込まれ、遺伝子発現することができるため、肺がんに対するワクチン開発へ応用可能である。また、siRNAへも応用できたため、肺がん治療薬としても期待される。既存の経口剤や注射薬に加え、新たな投与経路として吸入型のがん治療薬の開発へ発展できる可能性があると考えている。さらに、他の肺疾患にも応用できる可能性もあるため、幅広い医療貢献が期待できる。