Intracellular distribution of lipids and encapsulated model drugs from cationic liposomes with different uptake pathways

Masato Takikawa, Mizuki Fujisawa, Kazuma Yoshino, Shinji Takeoka

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Aim: The uptake pathway of liposomes into cells is mainly via endocytosis or membrane fusion; however, the relationship between the uptake pathway and the intracellular pharma-cokinetics of the liposome components remains unclear. This study aimed at revealing the relationship by using cationic liposomes having similar physical properties and different uptake pathways. Materials and Methods: We prepared cationic liposomes composed of amino acid-type lipids, K3C14 and K3C16, which have different uptake pathways by a hydration method, and fluorescently modified them by encapsulating FITC-dextran and surface conjugation with Alexa Fluor® 488 (AF488). Then, we investigated their intracellular distribution in HeLa cells over time. Results: The liposomes had similar physical properties and did not cause significant cell mortality after treatment for 180 min. The delivery rate and efficiency of encapsulated FITC-dextran with the fusogenic K3C16 liposomes were 3 and 1.6 times higher, respectively, than with the endocytic K3C14 liposomes. FITC-dextran molecules delivered with K3C16 lipo-somes were observed throughout the cytosolic space after 10 min, while those delivered with K3C14 liposomes were mainly observed as foci and took 60 min to diffuse into the cytosolic space. K3C14 lipids modified with AF488 were distributed mostly in the cytosolic space. In contrast, fluorescently labeled K3C16 lipids were colocalized with the plasma membrane of 50% of the HeLa cells after 10 min and were gradually internalized intracellularly. Conclusion: Fusogenic K3C16 liposomes internalized into HeLa cells faster than endocytic K3C14 liposomes, and their components differently distributed in the cells.

本文言語English
ページ(範囲)8401-8409
ページ数9
ジャーナルInternational Journal of Nanomedicine
15
DOI
出版ステータスPublished - 2020

ASJC Scopus subject areas

  • 生物理学
  • バイオエンジニアリング
  • 生体材料
  • 薬科学
  • 創薬
  • 有機化学

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