Cited by 19Nanoparticle-Based Drug DeliveryRNA Interference and Gene DeliveryExtracellular vesicles in disease

Investigation of enhanced intracellular delivery of nanomaterials modified with novel cell-penetrating zwitterionic peptide-lipid derivatives

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Sugimoto, Yuri, Suga, Tadaharu, Umino, Mizuki, Yamayoshi, Asako, Mukai, Hidefumi, Kawakami, Shigeru·2023·Drug Delivery

Abstract

Functionalized drug delivery systems have been investigated to improve the targetability and intracellular translocation of therapeutic drugs. We developed high functionality and quality lipids that met unique requirements, focusing on the quality of functional lipids for the preparation of targeted nanoparticles using microfluidic devices. While searching for a lipid with high solubility and dispersibility in solvents, which is one of the requirements, we noted that KK-(EK)4-lipid imparts nonspecific cellular association to polyethylene glycol (PEG)-modified (PEGylated) liposomes, such as cell-penetrating peptides (CPPs). We investigated whether KK-(EK)4-lipid, which has a near-neutral charge, is a novel CPP-modified lipid that enhances the intracellular translocation of nanoparticles. However, the cellular association mechanism of KK-(EK)4-lipid is unknown. Therefore, we synthesized (EK)n-lipid derivatives based on the sequence of KK-(EK)4-lipid and determined the sequence sites involved in cellular association. In addition, KK-(EK)4-lipid was applied to extracellular vesicles (EVs) and mRNA encapsulated lipid nanoparticles (mRNA-LNPs). KK-(EK)4-lipid-modified EVs and mRNA-LNPs showed higher cellular association and in vitro protein expression, respectively, compared to unmodified ones. We elucidated KK-(EK)4-lipid to have potential for applicability in the intracellular delivery of liposomes, EVs, and mRNA-LNPs.

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Crossref · 10.1080/10717544.2023.2191891

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  • Application of KK-(EK)4-lipids to exosomes and lipid nanoparticles encapsulating mRNA increased cellular association and enhanced protein expression in vitro for modified exosomes and mRNA-LNPs, respectively, compared to unmodified nanocarrier.

    “Application of KK-(EK)4-lipids to exosomes and lipid nanoparticles encapsulating mRNA increased cellular association and enhanced protein expression in vitro for modified exosomes and mRNA-LNPs, respectively, compared to the unmodified nanocarrier.”
  • KK-(EK)4-lipid has potential for liposomes, exosomes and mRNA-LNP intracellular delivery.

    “These findings demonstrate the potential of KK-(EK)4-lipid for liposomes, exosomes and mRNA-LNP intracellular delivery, proving its versatility and promise in this regard [126].”

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Authors
Sugimoto, Y., Suga, T., Umino, M., Yamayoshi, A., Mukai, H., & Kawakami, S.
Affiliations
  • Nagasaki University (JP)
  • RIKEN Center for Biosystems Dynamics Research (JP)
Corresponding author
Kawakami, Shigeru
Venue
Drug Delivery
Published
2023-03-25
Volume
30
Issue
1
Pages
2191891-2191891
ISSN
  • 1071-7544 (ISSN-L)
  • 1521-0464
OpenAlex
W4360939375
Cited by
19
References
40
Citations by year
2026: 7 · 2025: 5 · 2024: 4 · 2023: 3
FWCI
1.21
Type
journal article
Language
en
Open access
Locations
  • Drug Delivery (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • JSPS KAKENHI (21H03818)
  • Canon Foundation
  • Uehara Memorial Foundation
  • Smoking Research Foundation
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
cell-penetrating peptides, zwitterionic lipids, lipid modification, intracellular delivery, PEGylated liposomes, extracellular vesicles, mRNA lipid nanoparticles, protein expression
MeSH terms
Lipids, Liposomes, RNA, Messenger, Drug Delivery Systems, Nanoparticles, Cell-Penetrating Peptides

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