Copper-free click functionalization of glucose-derived carbon spheres for tumor targeting
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MRS Advances © 2019 Materials Research Society DOI: 10.1557/adv.2019.488
Copper-free click functionalization of glucosederived carbon spheres for tumor targeting Isabel Gessner†, Eva Krakor†, Sarah Styrnol†, Annika Klimpel‡, Ines Neundorf‡, Sanjay Mathur†,* †
Institute of Inorganic Chemistry, University of Cologne, Greinstr. 6, 50939 Cologne, Germany
‡
Institute of Biochemistry, University of Cologne, Zuelpicher Str. 47, 50674 Cologne, Germany
*corresponding author: [email protected]
Abstract
The dysfunctional metabolism of glucose in cancer cells represents a new avenue for cancer targeting based on sugar-derived carriers. Here, glucose-derived carbon spheres (CS) were prepared through a simple hydrothermal method, yielding highly homogenous spherical particles that exhibited excellent stability in aqueous solution. The abundant presence of surface hydroxyl functionalities was used for a subsequent condensation of an amino silane that was the basis for further covalent coupling strategies. CS were modified with a cyclooctyne derivative providing a highly selective binding site for copper-free click reactions. Moreover, the surface modification of CS with a dye-label allowed for their intracellular detection revealing a preferential uptake of CS, compared to silica particles, in tumor cells. These results thus demonstrate the highly promising potential of glucose-derived particles for tumor targeting applications and their efficient surface modification.
INTRODUCTION In order to fuel the uncontrolled cell proliferation and growth of cancer cells, metastatic cancers have shown to possess a remarkably higher glucose consumption than normal tissues.[1] In many cancer types, aerobic glycolysis was observed to become predominant even in the presence of oxygen, a phenomenon called the Warburg effect. This leads to a toxic and acidic microenvironment for surrounding healthy tissue and offers significant growth advantages for cancer cells.[2] Autoradiographic studies on the
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well-known positron emission tomography (PET) tracer 18F-FDG, a radiolabeled glucose derivative, revealed that elevated expression levels of glucose transporter Glut-1 and Glut-3 as well as enhanced activity levels of hexokinase-II (HK-II) are mainly contributing to the accumulation of glucose in cancerous cells. [3] This dysfunctional metabolism of cancer cells has become of increasing interest for directing anticancer therapeutics to tumor tissues.[4] In this context, Venturelli and co-workers demonstrated that glucose coated magnetic particles were internalized into breast cancer cells via Glut1 based transport, indicating that glucose nanostructures could potentially target cancer cells.[5] Aside from their material composition, the surface modification of nanocarriers is essential to expand the
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