Active Targeting of Dendritic Polyglycerols for Diagnostic Cancer Imaging.


Journal

Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338

Informations de publication

Date de publication:
02 2020
Historique:
received: 03 09 2019
revised: 15 11 2019
pubmed: 28 12 2019
medline: 7 5 2021
entrez: 28 12 2019
Statut: ppublish

Résumé

Active tumor targeting involves the decoration of nanomaterials (NMs) with oncotropic vector biomolecules that selectively recognize certain antigens on malignant cells or in the tumor microenvironment. This strategy can facilitate intracellular uptake of NM through specific interactions such as receptor-mediated endocytosis and can lead to prolonged retention in the malignant tissues by preventing rapid efflux from the tumor. Here, the design of actively targeting, renally excretible bimodal dendritic polyglycerols (dPGs) for diagnostic cancer imaging is described. Single-domain antibodies (sdAbs) specifically binding to the epidermal growth factor receptor (EGFR) are employed herein as targeting warheads owing to their small size and high affinity for their corresponding antigen. The dPGs equipped with EGFR-targeting feature are compared head-to-head with their nontargeting counterparts in terms of interaction with EGFR-overexpressing cells in vitro as well as accumulation at receptor-positive tumors in vivo. Experimental results reveal a higher specificity and preferential tumor accumulation for the α-EGFR dPGs, resulting from the introduction of active targeting capabilities on their backbone. These results highlight the potential for improving the tumor uptake properties of dPGs by strategic use of sdAb functionalization, which can ultimately prove useful to the development of ultrasmall NM with highly specific tumor accumulation.

Identifiants

pubmed: 31880080
doi: 10.1002/smll.201905013
doi:

Substances chimiques

Polymers 0
Single-Domain Antibodies 0
polyglycerol 25618-55-7
EGFR protein, human EC 2.7.10.1
ErbB Receptors EC 2.7.10.1
Glycerol PDC6A3C0OX

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1905013

Informations de copyright

© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Auteurs

Kritee Pant (K)

Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf, Bautzner Landstrasse 400, D-01328, Dresden, Germany.

Christin Neuber (C)

Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf, Bautzner Landstrasse 400, D-01328, Dresden, Germany.

Kristof Zarschler (K)

Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf, Bautzner Landstrasse 400, D-01328, Dresden, Germany.

Johanna Wodtke (J)

Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf, Bautzner Landstrasse 400, D-01328, Dresden, Germany.

Sebastian Meister (S)

Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf, Bautzner Landstrasse 400, D-01328, Dresden, Germany.

Rainer Haag (R)

Organische Chemie, Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, D-14195, Berlin, Germany.

Jens Pietzsch (J)

Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf, Bautzner Landstrasse 400, D-01328, Dresden, Germany.
School of Science, Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, D-01062, Dresden, Germany.

Holger Stephan (H)

Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden - Rossendorf, Bautzner Landstrasse 400, D-01328, Dresden, Germany.

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