Carbohydrate nanonets for cancer theranostics

last updated: 2019-02-13
ProjectCHEM2NATURE :: publications list
TitleCarbohydrate nanonets for cancer theranostics
Publication TypeComunication - Oral
Year of Publication2017
AuthorsBrito A., Soares da Costa D., Carvalho A. F., Reis R. L., Pires R. A., and Pashkuleva I.

The tumors’ development is related with accelerated cellular metabolism and therefore an increased glucose uptake.[1, 2] Thus, the development of mechanisms and compounds that interfere with glucose turnover is a way to elaborate novel anticancer therapies. An example is the aerobic blockage of glycolysis in tumor cells that has given quite promising results. However, we are still far away of creating effective and selective treatments using this approach. Few years ago, a new strategy for selective cancer therapy has emerged – biocatalytic self-assembly. It is based on self-assembly process that is triggered by enzyme(s) overexpressed by cancer cells, e.g. alknaline phosphatase (ALP).[3] The design of the self-assembling units, so-called gelators, is crucial in this approach. So far, derivatives of enzyme-sensitive peptides’ amphiphiles have been mainly used. These compounds are internalized by the cells, where upon the action of different intracellular enzymes are transformed into toxic nanofibers killing the host cell. Recently, we suggested an alternative gelator - a simple glucose derivative (N-(fluorenylmethoxycarbonyl)-glucosamine-6-phosphate) and demonstrated its potential for treatment of osteosarcoma.[4] Besides the promising results, various mechanisms can be involved in the observed cancer cells death. Herein, we investigated several possible modus operandi of the developed by us glucose-based gelator. We demonstrate that this aromatic carbohydrate amphiphile differs by the peptides ones – its in situ conversion and self-assembly is catalyzed mainly by membrane-bound ALP. As a result, the nanofibers/hydrogel is formed in the pericellular space but not intracellular as observed for peptide amphiphiles. We show that this process is cell specific: apoptosis was induced for osteosarcoma (SaOs2) and hepatocellular carcinoma cells (HepG2) that overexpress membrane-bound ALP while other type of cells (e.g., ATDC5) with low expression of this protein are not affected by the addition of the glucose amphiphile. These results are in agreement with the expression of several glucose transposters (GLUTs) by the studies cells indicating that the selective apoptosis is probably induced by two synergistic mechanisms: formation of pericellular net that traps selectively the ALP overexpressing cells and blockage of GLUTs, i.e. the glucose transport, in these cells. 

Conference NameCHEM2NATURE Second School
Date Published2017-06-05
Conference LocationPorto, Portugal
Keywordscancer theranostics, carbohydrate nanonet
Peer reviewedno

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