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
Influence of liposome composition on cellular drug delivery and therapeutic effect mediated by Nuclisome-particles
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
Department of Medicine, Division of Haematology-Oncology, Cancer research institute, University of California San Fransisco, USA.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
National Category
Other Basic Medicine
Identifiers
URN: urn:nbn:se:uu:diva-158994OAI: oai:DiVA.org:uu-158994DiVA: diva2:441986
Available from: 2011-09-20 Created: 2011-09-20 Last updated: 2011-11-04
In thesis
1. Two-Step Targeting for Effective Radionuclide Therapy: Preclinical Evaluation of 125I-labelled Anthracycline Delivered by Tumour Targeting Liposomes
Open this publication in new window or tab >>Two-Step Targeting for Effective Radionuclide Therapy: Preclinical Evaluation of 125I-labelled Anthracycline Delivered by Tumour Targeting Liposomes
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

For the treatment of cancer, Auger-electron emitting radionuclides are strongly dependent on their close proximity to DNA to utilize the local therapeutic potential of the Auger electrons. This thesis investigates a two-step targeting approach that uses targeting liposomes for the delivery of an Auger-electron emitter, 125I, coupled to a DNA-binding compound, Comp1, to the tumour-cell DNA. In the first step the liposome targets overexpressed cell-surface receptors. Receptors belonging to epidermal growth factor receptor (EGFR) family are overexpressed in a number of different cancers and are therefore suitable targets. The second step is transportation of the radionuclide to the cell nucleus utilizing a DNA-binding compound. The DNA-binder used in this thesis is a daunorubicin derivative called Comp1. Papers I and II are in vitro characterizations of the targeting liposomes. Both EGFR- and HER2-targeting liposomes delivered 125I-Comp1 receptor specifically to tumour cells, and were efficient in decreasing growth of cultured tumour cells. Paper II also included a biodistribution of 125I-Comp1 delivered by HER2-targeting liposomes in tumour-bearing mice. The results gave a time-dependent uptake in tumours differed from when non-targeting liposomes encapsulating 125I-Comp1 were given. Paper III investigates the therapeutic effect of 125I-Comp1 delivered by HER2-targeting liposomes, in an animal model that mimics a situation of disseminated tumour cells in the abdomen. 125I-Comp1 delivered by HER2-targeting liposomes effectively prolonged survival of the mice in a dose-dependent relation. Several mice in the groups receiving the highest doses were tumour-free at the end of the study. Paper IV compares different lipid compositions of the liposomes with respect to leakage, cellular uptake and therapeutic efficacy of delivered 125I-Comp1on cultured cells. Liposomes containing sphingomyelin or dihydrosphingomyelin retained drug more efficiently and exhibited more receptor specific delivery properties than distearoylglycerophosphatidylcholine (DSPC) containing liposomes. However, it was the DSPC-containing liposomes that displayed best growth inhibition on cultured tumour cells. The thesis concludes that 125I-Comp1 delivered by targeting liposomes is a promising candidate for effective radionuclide therapy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 100 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 708
Keyword
radionuclide, Auger electrons, liposomes, targeting, tumour therapy
National Category
Other Basic Medicine
Research subject
Biomedical Radiation Science
Identifiers
urn:nbn:se:uu:diva-159365 (URN)978-91-554-8172-8 (ISBN)
Public defence
2011-11-12, Rudbecksalen, Dag Hammarskjölds väg 20, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-10-21 Created: 2011-09-29 Last updated: 2011-11-04Bibliographically approved

Open Access in DiVA

No full text

By organisation
Biomedical Radiation SciencesPhysical ChemistryOrganic Pharmaceutical Chemistry
Other Basic Medicine

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 54816 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