The establishment of drug-delivery system and the 3D-microimaging of intra-cerebral pharmacokinetics in malignant glioma

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15554
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nagasaki University
• Principal Investigator: Yoshida Michiharu 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (00795437)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: glioblastoma / focused ultrasound / micro-bubbles / lipid nanoparticles / drug derivery system / mRNA / doxorubicin / malignant glioma

Outline of Final Research Achievements

mRNA encapsulated-lipid nanoparticles (mRNA-LNPs) can hardly express foreign proteins in brain because they cannot spontaneously cross the blood-brain barrier (BBB). Focused ultrasound (FUS)/microbubbles-assisted BBB opening is an emerging technology that can transiently enhance BBB permeability of substances. The FUS/microbubbles-assisted BBB opening was investigated for delivery of mRNA-LNPs to brain via intravenous route. The exogenous protein (luciferase) expression by mRNA-LNPs specifically at the FUS-irradiated side of brain occurred only when FUS and microbubbles were applied to open the BBB. This exogenous protein expression was faster but shorter than in the case of plasmid DNA delivery. In addition, foreign protein expression was observed in microglia, while no expression was found in astrocytes or neurons. These results add mRNA-LNPs, which are now attracting particular attention, to the lineup of nanoparticles delivered by such BBB opening.

Free Research Field

脳腫瘍治療

Academic Significance and Societal Importance of the Research Achievements

mRNAがLNP封入により血中で安定して維持され、FUS照射とBL製剤によって脳内の照射部位選択的にBBBを超えて送達可能であるという、脳内へのDDSにおける2つの大きな障壁を克服する新知見を得ることが出来た。
今後は、薬剤封入技術を応用し、悪性神経膠腫モデルに対して抗癌剤（DOX）封入リポソームやmRNA封入LNPをFUSとBLにより脳内送達し抗腫瘍効果を得ることで、化学療法の治療効果の向上を期待できる可能性がある。