Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles

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dc.identifier.uri http://dx.doi.org/10.15488/3435
dc.identifier.uri http://www.repo.uni-hannover.de/handle/123456789/3465
dc.contributor.author Engelberg, Shira
dc.contributor.author Modrejewski, Julia
dc.contributor.author Walter, Johanna-Gabriela
dc.contributor.author Livney, Yoav D.
dc.contributor.author Assaraf, Yehuda G.
dc.date.accessioned 2018-06-08T11:57:13Z
dc.date.available 2018-06-08T11:57:13Z
dc.date.issued 2018
dc.identifier.citation Engelberg, S.; Modrejewski, J.; Walter, J.G.; Livney, Y.D.; Assaraf, Y.G.: Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles. In: Oncotarget 9 (2018), Nr. 30, S. 20993-21006. DOI: https://doi.org/10.18632/oncotarget.24772
dc.description.abstract Lung cancer is the leading cause of cancer mortality worldwide, resulting in 88% deaths of all diagnosed patients. Hence, novel therapeutic modalities are urgently needed. Single-stranded oligonucleotide-based aptamers (APTs) are excellent ligands for tumor cell targeting. However, the molecular mechanisms underlying their internalization into living cells have been poorly studied. Towards the application of APTs for active drug targeting to cancer cells, we herein studied the mechanism underlying S15-APT internalization into human non-small cell lung cancer A549 cells. We thus delineated the mode of entry of a model nanomedical system based on quantum dots (QDs) decorated with S15-APTs as a selective targeting moiety for uptake by A549 cells. These APT-decorated QDs displayed selective binding to, and internalization by target A549 cells, but not by normal human bronchial epithelial BEAS2B, cervical carcinoma (HeLa) and colon adenocarcinoma CaCo-2 cells, hence demonstrating high specificity. Flow cytometric analysis revealed a remarkably low dissociation constant of S15-APTs-decorated QDs to A549 cells (Kd = 13.1 ± 1.6 nM). Through the systematic application of a series of established inhibitors of known mechanisms of endocytosis, we show that the uptake of S15-APTs proceeds via a classical clathrin-dependent receptor-mediated endocytosis. This cancer cell-selective mode of entry could possibly be used in the future to evade plasma membranelocalized multidrug resistance efflux pumps, thereby overcoming an important mechanism of cancer multidrug resistance. © Engelberg et al. eng
dc.language.iso eng
dc.publisher S.l. : Impact Journals LLC
dc.relation.ispartofseries Oncotarget 9 (2018), Nr. 30
dc.rights CC BY 3.0
dc.rights.uri https://creativecommons.org/licenses/by/3.0/
dc.subject Aptamers eng
dc.subject Clathrin-mediated endocytosis eng
dc.subject Lung cancer eng
dc.subject Multidrug resistance eng
dc.subject Targeted delivery eng
dc.subject aptamer eng
dc.subject clathrin eng
dc.subject nanoparticle eng
dc.subject quantum dot eng
dc.subject A-549 cell line eng
dc.subject Article eng
dc.subject BEAS-2B cell line eng
dc.subject Caco-2 cell line eng
dc.subject cancer cell eng
dc.subject cancer resistance eng
dc.subject cell membrane eng
dc.subject controlled study eng
dc.subject dissociation constant eng
dc.subject drug binding eng
dc.subject drug selectivity eng
dc.subject drug specificity eng
dc.subject drug targeting eng
dc.subject endocytosis eng
dc.subject female eng
dc.subject flow cytometry eng
dc.subject HeLa cell line eng
dc.subject human eng
dc.subject human cell eng
dc.subject internalization eng
dc.subject male eng
dc.subject multidrug resistance eng
dc.subject.ddc 610 | Medizin, Gesundheit ger
dc.title Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles
dc.type article
dc.type Text
dc.relation.issn 1949-2553
dc.relation.doi https://doi.org/10.18632/oncotarget.24772
dc.bibliographicCitation.issue 30
dc.bibliographicCitation.volume 9
dc.bibliographicCitation.firstPage 20993
dc.bibliographicCitation.lastPage 21006
dc.description.version publishedVersion
tib.accessRights frei zug�nglich


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