uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
EGF-targeting lipodisks for specific delivery of cationic amphiphilic peptides to tumour cells
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
(English)Manuscript (preprint) (Other academic)
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-305375OAI: oai:DiVA.org:uu-305375DiVA: diva2:1037588
Available from: 2016-10-17 Created: 2016-10-17 Last updated: 2016-11-11
In thesis
1. Development of lipodisks as carriers for cationic amphiphilic peptides
Open this publication in new window or tab >>Development of lipodisks as carriers for cationic amphiphilic peptides
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Antibiotics have made a tremendous contribution to mankind. They are one of the most successful medicines in human history. However, more and more bacterial strains develop resistance and the risk to public health can hardly be overstated. New types of antibiotics are urgently needed. Antimicrobial peptides (AMPs) have emerged as potential antibiotics because of their broad-spectrum activities and non-conventional mechanism of action. More recently, they have also received attention as promising anticancer agents. The clinical and commercial development of AMPs as a new generation of antibiotics and anticancer drugs is hampered, however, by issues concerning the toxicity, specificity and stability of the peptides.

The aim of this thesis has been to explore if formulation in a novel type of nanocarriers, referred to as lipodisks, can be used to increase the therapeutic potential of AMPs as antimicrobial and anticancer agents. Focus has been on AMPs classified as cationic amphiphilic peptides.

Encouragingly, the data presented suggests that the therapeutic potential of the AMP melittin as an antimicrobial and anticancer agent can be substantially increased by formulation in lipodisks. When formulated in the lipodisk, melittin is protected against enzymatic degradation. The lipodisk also offer a slow-release effect that sustains the bacterial cell-killing effect. We also show that specific delivery of melittin to tumour cells can be obtained by formulating the peptide in small EGF-targeting lipodisks.

Melittin contains a tryptophan residue and its interaction with lipodisks can be characterized by means of fluorimetric binding assays. In order to investigate the binding behavior also for peptides that lack intrinsic fluorescence, we developed a method based on measurements using the QCM-D technique. Studies using this, and other techniques, confirmed that it is a general behavior for cationic amphiphilic peptides to preferentially bind to the highly curved rim of lipodisks. Results of our binding studies show that the peptide to lipid ratio in the lipodisks can be tuned and optimized by varying the size and charge of the disks.

Taken together, the findings in this thesis point towards PEG-stabilized lipodisks as promising nanocarriers for antibacterial and anticancer peptides.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 48 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1442
National Category
Natural Sciences Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-305443 (URN)978-91-554-9729-3 (ISBN)
Public defence
2016-12-02, B41, BMC, Husargatan 3, Uppsala, 10:15 (Swedish)
Opponent
Supervisors
Available from: 2016-11-11 Created: 2016-10-18 Last updated: 2016-11-16

Open Access in DiVA

No full text

Authority records BETA

Reijmar, KarinEdwards, Katarina

Search in DiVA

By author/editor
Ahlgren, SaraReijmar, KarinEdwards, Katarina
By organisation
Analytical Chemistry
Physical Chemistry

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 540 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf