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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - GlycoImaging (Imaging and detection of tumor-associated glycan structures on tumor cells)

Teaser

Summary

A major challenge in the war against cancer is to find ways to diagnose and treat the disease at an early stage. Cancer occurs through a multistage process where cells are transformed to malignant tumors. Of essence is to discover the tumor at an early stage where the cancer is still curable. This calls for sensitive and effective diag-nostic tools that can sense the cellular state early in the process. In GlycoImaging we will address this need while exploiting novel exciting molecularly imprinted probes targeting tumor specific glycans. These â€œplastic anti-bodiesâ€ will be developed and used for real-time visualization of cellular cancer biomarkers and in low-cost clinical diagnostics. 5 research groups, spread across 5 universities and institutes, and 2 industrial partners in 4 different countries have come together to train a new generation of chemists/biologists through the PhD training network. Thereby we have created a highly interdisciplinary research-training network with ambitious scientific goals and an attractive training program. GlycoImaging will aim to develop and implement highly promising glycan specific probes in clinically relevant cancer diagnostics technologies. We will develop glycan-specific nano-probesâ€”abbreviated SAMIPs (MIPs against sialic acid)â€”alongside digital holography for real-time visualization of cancer biomarkers and use in low-cost clinical diagnostics, glycan-specific cell separations and in life science and education.

Work performed

Summary of main results:

The protocols for the synthesis of fluorescent molecularly imprinted polymers (MIPs) against the human sugar structure sialic acid (SA), SA-MIPs, have been developed, optimized and evaluated. The flow cytometry method show that SA-MIPs can target and bind to cancer cells by detecting a fluorescent signal on the cancer cell. With fluorescence microscopy, the binding of the SA-MIps to cancer cells can be visualized. To make sure that the SA-MIPs bind specifically to the SA-structures on the cancer cells, specificity studies have been performed with flow cytometry and fluorescence microscopy.

In addition, the protocols for the synthesis of non-human sialic acid (SA)/Neu5Gc and control fluorescent non-imprinted MIPs, SA-NIPs, have been optimized and evaluated. The synthesis of novel fluorophores in MIPs against human SA, SA-MIPs, have been optimized and evaluated to meet the need for in vivo applications.

Digital holographic microscopy (DHM) for cellular measurements in 3D, with or without MIPs, have been used analyze cancer cells. For that purpose, non-fluorescent MIPs against human SA, SA-MIPs, have been optimized and evaluated, since DHM is monitored non-fluorescently.

Genetically engineered cell libraries are generated of the glycosaminoglycan (GAG) species chondroitin sulfate and heparin sulfate. These cells will be used for future GAG-specific MIPs synthesized by other research groups.
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Preparations have been done in animal models to be able to study in vivo MIP-targeting to cancer cells in mice, using SA-MIPs with different fluorophores.

Final results

The GlycoImaging project emphasises on highly needed sensitive, but low cost diagnostic tools and bring together expertise in the field of cancer, biomarkers, glycobiology and imaging. The project will strongly impact on the researchers professional development preparing for a successful career, where the European industry also will make benefits. High-quality ESR training with a commitment to train 8 ESRs toward a PhD degree is the central pillar of the project. The training has a special focus on key scientific, business and entrepreneurial skills that are currently lacking in todayÂ´s European work force. The demand for researchers with this broad set of skills is widespread in both industry and academia. Individual career perspectives will depend on the ESRs specific tasks in GlycoImaging and directly support:
- specific targeting of rare cancer glycosylation motifs by the use of novel MIPs,
- enhanced understanding of the wide spectrum of alterations in glycosylation for the development and progression of neoplastic (cancer) diseases,
- Improved knowledge of glycan-based therapy against aggressive cancer,
- Improvement of the health of millions of new cancer cases worldwide,
- the innovation capacity through new methodology by integrating cellular 3D imaging, molecular imprinting technology and sensitive column separation.