New Gels Expected to Help in the Development of Anti-cancer Drugs

29 August 2019

Singapore – Researchers from A*STAR’s Institute of Bioengineering and Nanotechnology (IBN) have developed a customisable hydrogel that cultivates patient-derived tumour organoids which can better mimic the original. This has the potential to pave the way towards developing more disease-relevant models for cancer drug discovery, and hyper-personalised cancer treatments.

The use of patient-derived tumour organoids is becoming increasingly important in cancer drug development, especially since conventional cancer cell lines offer limited predictive value in drug discovery. Tumour organoids closely model key features of the native tumour tissue, so that tests for the efficacy of potential cancer drugs would be more accurate.

Tumour organoids are typically grown within a biological hydrogel matrix of animal origin, regardless of the type of tumour being studied. The use of such a generic matrix, which is mechanically soft and has a highly complex biochemical composition, limits researchers’ abilities to mimic the unique physical and biochemical properties of the original patient tumour.

To address these issues, IBN researchers have fabricated a more customisable type of synthetic hydrogel that can be tailored to unique tumour types. Using chemically-modified biomolecules to systematically control both the biochemical and mechanical properties of the hydrogel, IBN researchers found that a single biochemical component (gelatin), high matrix stiffness, and a low-oxygen environment was sufficient to support patient-derived tumour organoid survival, growth and metabolism. The research team, led by IBN Team Leader and Principal Research Scientist Dr Motoichi Kurisawa, established the feasibility of such an approach using patient-derived colorectal cancer (CRC) tumour organoids. CRC is one of the major cancers in Singapore and there is currently no 3D culture system that is designed specifically for CRC tumour organoids.

Researchers from IBN

“We demonstrated that CRC tumour organoids grown in customised hydrogels supported drug response and sensitivity similar to those grown in conventional animal-derived matrices,” said Dr Kurisawa. “This highlights the potential role of the matrix in governing tumour organoid responses to clinically relevant drugs,” he added.

Dr Ichiro Hirao, Covering Executive Director of A*STAR’s IBN, said: “The IBN research team wants to overcome the limitations facing current tools in cancer biology and cancer drug discovery. We anticipate that this work will contribute to the development of customised matrices with tissue-specific properties for culturing other types of patient-derived tumour organoids. This will advance the science in this field for the wider research community, and lead to better healthcare outcomes through aiding the development of disease-relevant models for cancer drug discovery.”

The research results were published in the journal Biomaterials on 31 July 2019.

Reference:

S. Ng, W. J. Tan, M. M. X. Pek, M. H. Tan, M. Kurisawa, “Mechanically and chemically defined hydrogel matrices for patient-derived colorectal tumor organoid culture”, Biomaterials (2019) doi.org/10.1016/j.biomaterials.2019.119400. See article.

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About the Institute of Bioengineering and Nanotechnology

The Institute of Bioengineering and Nanotechnology (IBN) is the world’s first bioengineering and nanotechnology research institute. Established in 2003, IBN’s mission is to conduct multidisciplinary research across science, engineering, and medicine for breakthroughs to improve healthcare and quality of life. IBN’s research activities are focused on Nanomedicine and Biomaterials, Synthetic Xenobiology and Biosystems, Tissue and Organoid Models, and Green and Safe Biomaterials. The Institute has published over 1,320 papers in leading scientific journals, filed over 660 active patents and patent applications on its inventions, and established 12 spin-off companies. For more information on IBN, please visit www.a-star.edu.sg/ibn.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.

As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.

We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and research entities, the wider research community and industry. A*STAR’s R&D activities span biomedical sciences and physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.

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