dc.contributor.author | Iversen, Tore G | |
dc.contributor.author | Frerker, Nadine | |
dc.contributor.author | Sandvig, Kirsten | |
dc.date.accessioned | 2015-10-20T10:56:20Z | |
dc.date.available | 2015-10-20T10:56:20Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Journal of Nanobiotechnology. 2012 Jul 31;10(1):33 | |
dc.identifier.uri | http://hdl.handle.net/10852/47187 | |
dc.description.abstract | Background
There is a huge effort in developing ligand-mediated targeting of nanoparticles to diseased cells and tissue. The plant toxin ricin has been shown to enter cells by utilizing both dynamin-dependent and -independent endocytic pathways. Thus, it is a representative ligand for addressing the important issue of whether even a relatively small ligand-nanoparticle conjugate can gain access to the same endocytic pathways as the free ligand.
Results
Here we present a systematic study concerning the internalization mechanism of ricinB:Quantum dot (QD) nanoparticle conjugates in HeLa cells. Contrary to uptake of ricin itself, we found that internalization of ricinB:QDs was inhibited in HeLa cells expressing dominant-negative dynamin. Both clathrin-, Rho-dependent uptake as well as a specific form of macropinocytosis involve dynamin. However, the ricinB:QD uptake was not affected by siRNA-mediated knockdown of clathrin or inhibition of Rho-dependent uptake caused by treating cells with the Clostridium C3 transferase. RicinB:QD uptake was significantly reduced by cholesterol depletion with methyl-β-cyclodextrin and by inhibitors of actin polymerization such as cytochalasin D. Finally, we found that uptake of ricinB:QDs was blocked by the amiloride analog EIPA, an inhibitor of macropinocytosis. Upon entry, the ricinB:QDs co-localized with dextran, a marker for fluid-phase uptake. Thus, internalization of ricinB:QDs in HeLa cells critically relies on a dynamin-dependent macropinocytosis-like mechanism.
Conclusions
Our results demonstrate that internalization of a ligand-nanoparticle conjugate can be dependent on other endocytic mechanisms than those used by the free ligand, highlighting the challenges of using ligand-mediated targeting of nanoparticles-based drug delivery vehicles to cells of diseased tissues. | |
dc.language.iso | eng | |
dc.rights | Iversen et al.; licensee BioMed Central Ltd. | |
dc.rights | Attribution 2.0 Generic | |
dc.rights.uri | http://creativecommons.org/licenses/by/2.0/ | |
dc.title | Uptake of ricinB-quantum dot nanoparticles by a macropinocytosis-like mechanism | |
dc.type | Journal article | |
dc.date.updated | 2015-10-20T10:56:20Z | |
dc.creator.author | Iversen, Tore G | |
dc.creator.author | Frerker, Nadine | |
dc.creator.author | Sandvig, Kirsten | |
dc.identifier.doi | http://dx.doi.org/10.1186/1477-3155-10-33 | |
dc.identifier.urn | URN:NBN:no-51289 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/47187/1/12951_2012_Article_200.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 33 | |