Because many anti-cancer drugs cause adverse side effects, molecular targeting techniques have been developed to specifically target drugs to tumor sites, minimizing their effects on healthy tissue. These techniques work by conjugating a small molecule or macromolecule to a cancer therapeutic. The small molecule or macromolecule then directs the therapeutic to the target site.

Molecular targeting techniques offer a broadly applicable platform for modulating the selectivity, specificity and other characteristics of a wide range of anti-cancer agents. However, an extensive array of small molecules and macromolecules is needed to provide specificity on an intracellular compartment, cell type or even organ level.

Because a fundamental characteristic of cancer cells is their increased uptake of glucose, sugar molecules may be an option. Glucose surrogates, such as the fluorescent molecule fluorodeoxyglucose (FDG), and glucose conjugates have been used successfully in cancer imaging and treatment. However, only a small set of “typical” sugars have been investigated for use in molecular targeting thus far.

UW-Madison researchers have developed a systematic platform for rapidly assessing the ability of a diverse range of sugars to enhance the uptake and selectivity of sugar conjugates. This invention may lead to the discovery of sugar molecules that improve the delivery of cancer therapeutics.

First, glycorandomization (see WARF reference numbers P04020US and P04455US) is used to generate a library of molecules that differ only by the sugars attached. Then each of these glycosylated molecules is contacted with cells, and their uptake into the cells is assessed relative to that of a corresponding molecule without the attached sugars. To determine selectivity, these sugar conjugates can be contacted with cells from different cell lines and their uptake compared to see if it is elevated in cells from a particular line.

Using this strategy, the researchers found that slight changes in sugar structure can lead to drastic changes in in vitro cellular uptake. They identified sugars that impart up to an eight-fold increase in selective uptake by tumor, rather than normal, cell lines. They also identified sugars that provide greater than a 10-fold increase in uptake as compared to the conventional sugars glucose, 2-deoxyglucose or FDG.

File Number: P08069US 

Other Information: See WARF reference number P04020US for more information on glycorandomization.

See WARF reference number P04455US for more information on neoglycorandomization.

See WARF reference number P08342US for additional compounds that can be used as research tools for studying sugar uptake.