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Cited by 23Nanoparticle-Based Drug DeliveryLipid Membrane Structure and BehaviorRNA Interference and Gene Delivery

Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles

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Utterström, Johanna, Barriga, Hanna M. G., Holme, Margaret N., Selegård, Robert, Stevens, Molly M., Aili, Daniel·2022·Bioconjugate Chemistry
DOI 10.1021/acs.bioconjchem.2c00115PMC PMC9026255
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Abstract

Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to trigger and control the release. Cholesterol is used in most liposomal drug delivery systems (DDS) to improve the stability of the formulation, but the activity of AMPs on cholesterol-rich membranes tends to be very low, complicating peptide-triggered release strategies. Here, we show a de novo designed AMP-mimetic peptide that efficiently triggers content release from cholesterol-containing lipid vesicles when covalently conjugated to headgroup-functionalized lipids. Binding to vesicles induces peptide folding and triggers a lipid phase separation, which in the presence of cholesterol results in high local peptide concentrations at the lipid bilayer surface and rapid content release. We anticipate that these results will facilitate the development of peptide-based strategies for controlling and triggering drug release from liposomal drug delivery systems.

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  • Human red blood cell membrane stabilisation is indicative of anti-inflammatory activity.

    “Human red blood cells (HRBCs) were used to evaluate membrane stabilisation potential, which is indicative of anti-inflammatory activity (Nguyen et al., 2026;Pinto et al., 2017;Utterström et al., 2022;Zhang et al., 2026).”

    From PHYTOCHEMICAL CHARACTERIZATION AND EVALUATION OF ANTIOXIDANT, ANTIMICROBIAL, ANTI-INFLAMMATORY, AND CYTOTOXIC ACTIVITIES OF SEQUENTIAL EXTRACTS FROM RIPE BANANA (MUSA PARADISIACA L.) PEEL (2026) · cites this paper as Utterström et al., 2022

    The Introduction (page not provided) mentions limiting hemolytic effects, while the Results and Discussion (page not provided) examine peptide effects on synthetic lipid vesicles. Neither passage connects human red blood cell membrane stabilisation with anti-inflammatory activity; searches for HRBCs, erythrocytes, hemolysis, and inflammation found no such connection. (LLM, conf=0.77)

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Cited by

Sorted by citations

Authors
Utterström, J., Barriga, H. M. G., Holme, M. N., Selegård, R., Stevens, M. M., & Aili, D.
Affiliations
  • Linköping University (SE)
  • Karolinska Institutet (SE)
Corresponding author
  • Holme, Margaret N.
  • Stevens, Molly M.
  • Aili, Daniel
ORCID
Venue
Bioconjugate Chemistry
Publisher
American Chemical Society (ACS)
Published
2022-04-01
Volume
33
Issue
4
Pages
736-746
ISSN
  • 1043-1802 (ISSN-L)
  • 1520-4812
DOI
10.1021/acs.bioconjchem.2c00115
PMC
PMC9026255
OpenAlex
W4220787330
Cited by
23
References
0
Citations by year
2026: 6 · 2025: 6 · 2024: 8 · 2023: 2 · 2022: 1
FWCI
1.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Bioconjugate Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DiVA (Linkoping University) (submittedVersion, other-oa)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • Royal Academy of Engineering (CiET2021\94)
  • Vetenskapsr?det (2017-04475)
  • Link?pings Universitet (2009-0097)
  • Knut och Alice Wallenbergs Stiftelse (KAW 2016.0231)
  • Rosetrees Trust
  • Stiftelsen f?r?Strategisk Forskning (FFL15-0026)
  • Cancerfonden (21 1603 Pj 01 H, CAN 2017/430)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
liposomal drug delivery, lipid phase separation, membrane-active peptides, peptide folding, controlled drug release, membrane perturbation
MeSH terms
Cholesterol, Lipid Bilayers, Liposomes, Peptides, Drug Delivery Systems

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