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dc.contributor.author
Yang, Yongkun
dc.contributor.author
Neef, Tobias
dc.contributor.author
Mittelholzer, Christian
dc.contributor.author
García Garayoa, Elisa
dc.contributor.author
Bläuenstein, Peter
dc.contributor.author
Schibli, Roger
dc.contributor.author
Aebi, Ueli
dc.contributor.author
Burkhard, Peter
dc.date.accessioned
2019-05-10T14:09:04Z
dc.date.available
2017-06-11T02:07:24Z
dc.date.available
2019-05-10T12:57:29Z
dc.date.available
2019-05-10T14:09:04Z
dc.date.issued
2013-11-12
dc.identifier.issn
1477-3155
dc.identifier.other
10.1186/1477-3155-11-36
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/76915
dc.identifier.doi
10.3929/ethz-b-000076915
dc.description.abstract
Background Because of the need to limit side-effects, nanoparticles are increasingly being studied as drug-carrying and targeting tools. We have previously reported on a scheme to produce protein-based self-assembling nanoparticles that can act as antigen display platforms. Here we attempted to use the same system for cancer-targeting, making use of a C-terminal bombesin peptide that has high affinity for a receptor known to be overexpressed in certain tumors, as well as an N-terminal polyhistidine tag that can be used for radiolabeling with technetium tricarbonyl. Results In order to increase circulation time, we experimented with PEGylated and unPEGylated varities typo particle. We also tested the effect of incorporating different numbers of bombesins per nanoparticle. Biophysical characterization determined that all configurations assemble into regular particles with relatively monodisperse size distributions, having peaks of about 33 – 36 nm. The carbonyl method used for labeling produced approximately 80% labeled nanoparticles. In vitro, the nanoparticles showed high binding, both specific and non-specific, to PC-3 prostate cancer cells. In vivo, high uptake was observed for all nanoparticle types in the spleens of CD-1 nu/nu mice, decreasing significantly over the course of 24 hours. High uptake was also observed in the liver, while only low uptake was seen in both the pancreas and a tumor xenograft. Conclusions The data suggest that the nanoparticles are non-specifically taken up by the reticuloendothelial system. Low uptake in the pancreas and tumor indicate that there is little or no specific targeting. PEGylation or increasing the amount of bombesins per nanoparticle did not significantly improve targeting. In particular, the uptake in the spleen, which is a primary organ of the immune system, highlights the potential of the nanoparticles as vaccine carriers. Also, the decrease in liver and spleen radioactivity with time implies that the nanoparticles are broken down and cleared. This is an important finding, as it shows that the nanoparticles can be safely used as a vaccine platform without the risk of prolonged side effects. Furthermore, it demonstrates that technetium carbonyl radiolabeling of our protein-based nanoparticles can be used to evaluate their pharmacokinetic properties in vivo.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
BioMed Central
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/
dc.subject
Self-assembly
en_US
dc.subject
Nanoparticle
en_US
dc.subject
Bombesin
en_US
dc.subject
Drug-targeting
en_US
dc.subject
Vaccine
en_US
dc.subject
Biodistribution
en_US
dc.subject
Technetium
en_US
dc.title
The biodistribution of self-assembling protein nanoparticles shows they are promising vaccine platforms
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 2.0 Generic
ethz.journal.title
Journal of Nanobiotechnology
ethz.journal.volume
11
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
J Nanobiotechnology
ethz.pages.start
36
en_US
ethz.size
10 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
London, UK
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03688 - Schibli, Roger / Schibli, Roger
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03688 - Schibli, Roger / Schibli, Roger
ethz.date.deposited
2017-06-11T02:10:30Z
ethz.source
ECIT
ethz.identifier.importid
imp5936515fdc75f47703
ethz.ecitpid
pub:121460
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-13T06:05:09Z
ethz.rosetta.lastUpdated
2019-05-10T14:09:13Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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