Development of lipid-like materials for RNA delivery based on intracellular environment-responsive membrane destabilization and spontaneous collapse

Hiroki Tanaka, Yu Sakurai, Jessica Anindita, Hidetaka Akita

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

Messenger RNA and small interfering RNA are attractive modalities for curing diseases by complementation or knock-down of proteins. For success of these RNAs, a drug delivery system (DDS) is required to control a pharmacokinetics, to enhance cellular uptake, to overcome biological membranes, and to release the cargo into the cytoplasm. Based on past research, developing nanoparticles that are neutrally charged have been the mainstream of their development. Also, the materials are further mounted with pH- and/or reducing environment-responsive units. In this review, we summarize progress made in the molecular design of these materials. We also focus on the importance of the hydrophobic scaffold for tissue/cell targeting, intracellular trafficking, and immune responses. As a practical example, the design concept of the SS-cleavable and pH-activated lipid-like material (ssPalm) and subsequent molecular modification tailored to the RNA-based medical application is discussed.

Original languageEnglish
Pages (from-to)210-226
Number of pages17
JournalAdvanced Drug Delivery Reviews
Volume154-155
DOIs
Publication statusPublished - 2020 Jan
Externally publishedYes

Keywords

  • immunity
  • lipid
  • mRNA
  • pharmacokinetics
  • siRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

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