mRNA薬剤送達のためのナノ粒子形状の重要性を解明(New pathway for mRNA drug delivery shows shape of things to come)

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2025-06-17 ロイヤルメルボルン工科大学(RMIT)

mRNA薬剤送達のためのナノ粒子形状の重要性を解明(New pathway for mRNA drug delivery shows shape of things to come)
A cubosome nanoparticle magnified more than 30,000 times, showing its lipids self-assembled into a cubic structure.

RMIT大学と大阪大学の研究チームは、立方格子構造を持つリピッドナノ粒子「カボソーム(cubosomes)」が、従来の層構造リポソームよりも最大8倍高い細胞取り込み効率を示すことを発見しました。Cubosomesは自己集合で形成され、細胞膜と直接融合する経路を持つため、分解されずに細胞内へ効率よく物質を運搬できます。この技術はmRNAワクチンや遺伝子治療薬の送達効率を飛躍的に高める可能性があり、今後の臨床応用が期待されています。

<関連情報>

脂質ナノ粒子の内部ナノ構造が多様な細胞内取り込み経路に影響を与える The Internal Nanostructure of Lipid Nanoparticles Influences Their Diverse Cellular Uptake Pathways

Sue Lyn Yap, Brendan Dyett, Alison J. Hobro, Han Nguyen, Nicholas I. Smith, Calum J. Drummond, Charlotte E. Conn, Nhiem Tran
Small  Published: 20 May 2025
DOI:https://doi.org/10.1002/smll.202500903

Abstract

Lipid nanoparticles have emerged as critical platforms for bioactive agent delivery, with their success in COVID-19 vaccines highlighting the urgent need to address gaps in understanding their biological interactions. Lyotropic liquid crystalline nanoparticles (LLCNPs) represent promising nanocarriers for bioactive agent delivery. In this study, it is revealed for the first time how internal nanostructures of LLCNPs – liposomes, cubosomes, hexosomes, and micellar cubosomes – influence their cellular uptake pathways. By isolating the effects of mesophase while maintaining consistent particle size, charge, and surface coating, it is demonstrated that non-lamellar LLCNPs, particularly cubosomes, significantly enhance cellular uptake via distinct endocytic and non-endocytic mechanisms. These nanoparticles predominantly utilize passive non-endocytic pathways, such as membrane fusion, bypassing endocytic recycling challenges faced by most nanomaterials, including lamellar liposomes. Among active endocytic pathways, macropinocytosis emerges as the dominant route for non-lamellar particles. The findings establish a direct link between LLCNP internal nanostructure and cellular internalization mechanisms, highlighting the critical role of mesophase design in optimizing nanocarrier performance. This knowledge enables the rational engineering of LLCNPs tailored to target specific uptake pathways, facilitating precision delivery for diverse therapeutic applications and addressing key barriers in intracellular drug transport.

生物化学工学
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