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Shedding New Light on Life Sciences: The Significance of Bioluminescence

By: Joyfull Widiyanto (BM ‘23) & Lynette Angelina (PH ‘23)

Jakarta, 27th September 2024 – When it comes to the development of biomedical research, many tools have been sourced from nature. From the use of biomaterials in treating medicine to the biomimicry of organism structures to improve biomedical devices, it is not a surprise that nature has been the biggest inspiration for pushing the boundaries of scientific research. One of the most powerful and important biomedical research tools must be from Mother Nature’s most alluring phenomenon: bioluminescence.

Bioluminescence is a form of chemiluminescence, a chemical reaction in living organisms that generates light without producing heat (San et al., 2023). Instead of using external sources to produce light like a fire, bioluminescence is created with the help of enzymes (Schramm & Weiß, 2024). Examples of organisms with bioluminescent properties are insects such as fireflies, bacteria, fungi, and marine animals (Yuan et al., 2024). 

There are two main principles behind bioluminescence. First is the bioluminescent system that involves the oxygenation of luciferin (a light-emitting molecule) with the aid of an enzyme called luciferase (Dunuweera et al., 2024). The subsequent reaction produces an excited-state molecule called oxyluciferin, emitting light when returning to its ground state (Schramm & Weiß, 2024). The other type of bioluminescence mechanism involves photoproteins. These proteins emit light when stimulated by changes in the protein environment with the use of oxidizing agents such as oxygen or hydrogen peroxide (Syed & Anderson, 2021). They catalyze bioluminescence by forming stable complexes with fluorescein under specific conditions; an example of such conditions would be calcium-rich environments (Yuan et al., 2024).

While it is a fact that bioluminescence is an essential trait of many organisms, its role in many scientific fields is indispensable. This is especially so in studies related to biomedicine. What makes bioluminescence unique from other emissions of light such as fluorescence is its ability to directly produce light without any absorption of sunlight or other external sources such as radiation (Dunuweera et al., 2024). As such, it is a perfect tool for marking and identifying biological components of living cells in organisms. Its application has been used to develop multiple analytical methods to analyze, leading to novel discoveries in life science (Dybas, 2024).

Bioimaging is one of the most essential tools in biomedical research with the rise in the use of bioluminescent components. Research has found several applications of bioluminescence, such as imaging for tumor diagnosis and monitoring, cell tracking, observation of cellular processes, and even the detection of drug processes (Yuan et al., 2024). The use of bioluminescence in bioimaging offers advantages such as accuracy in detecting physiological proteins at low concentrations, as well as its non-invasive and non-toxic nature (Araújo-Gomes et al., 2023; Yuan et al., 2024). Additionally, it has been recognized for its high biocompatibility with most cellular components (Xia et al., 2021). Thus, the benefits of using bioluminescent imaging have provided more opportunities for research.

One of the most relevant applications of bioimaging is in cancer research. Cancer cells and tumors could be monitored and detected through bioluminescence-induced microorganisms to help in therapy through bioimaging. Research by Yang et al. (2022) modified Salmonella typhimurium with firefly luciferase, which allows it to emit light. This is beneficial for photodynamic treatment (PDT), where bioluminescence is used as an internal light source to activate photosensitizers. It helps increase the efficacy of cancer treatment by colonizing tumors and producing light, particularly for larger or deeper-seated cancers where external light penetration is limited. 

Additionally, Bioluminescent Enzyme Immunoassay (BLEIA) is one of the applications of bioluminescence that offers a quick, adaptable, and highly effective way of identifying molecules in clinical samples. According to Samaki et al. (2012), firefly’s luciferase enzyme can be utilized in the BLEIA to detect norovirus (NV) strains rapidly and precisely for both symptomatic and asymptomatic persons. Compared to PCR, BLEIA test results can be generated more rapidly, making it suitable for routine diagnosis to prevent NV outbreaks. Furthermore, research done by Hall et al. (2021) found a newer and smaller luciferase variant called NanoLuc luciferase that provides a more rapid assay result. Due to its higher brightness and sensitivity, it could enhance the BLEIA method for greater flexibility in various applications like in vivo imaging. 

It is not a miracle that such a unique natural phenomenon could be utilized to a wide extent in the scientific field. However, current advancements have only touched the surface of the capabilities of bioluminescence. Therefore, further research about the stability and brightness of the bioluminescence proteins is needed to increase the efficiency of this method in the healthcare field. Furthermore, combining bioluminescence with other advanced technologies may create opportunities for novel clinical therapies.

References

Araújo-Gomes, N., Zambito, G., Johnbosco, C., Calejo, I., Leijten, J., Löwik, C., Karperien, M., Mezzanotte, L., & Teixeira, L. M. (2023). Bioluminescence imaging on-chip platforms for non-invasive high-content bioimaging. Biosensors and Bioelectronics, 237, 115510. https://doi.org/10.1016/j.bios.2023.115510

Dunuweera, A. N., Dunuweera, S. P., & Ranganathan, K. (2024). A Comprehensive Exploration of Bioluminescence Systems, Mechanisms, and Advanced Assays for Versatile Applications. Biochemistry Research International, 2024, e8273237. https://doi.org/10.1155/2024/8273237

Hall, M. P., Kincaid, V. A., Jost, E. A., Smith, T. P., Hurst, R., Forsyth, S. K., Fitzgerald, C., Ressler, V. T., Zimmermann, K., Lazar, D., Wood, M. G., Wood, K. V., Kirkland, T. A., Encell, L. P., Machleidt, T., & Dart, M. L. (2021). Toward a Point-of-Need Bioluminescence-Based Immunoassay Utilizing a Complete Shelf-Stable Reagent. Analytical Chemistry, 93(12), 5177–5184. https://doi.org/10.1021/acs.analchem.0c05074

Sakamaki, N., Ohiro, Y., Ito, M., Makinodan, M., Ohta, T., Suzuki, W., Takayasu, S., & Tsuge, H. (2012). Bioluminescent Enzyme Immunoassay for the Detection of Norovirus Capsid Antigen. Clinical and Vaccine Immunology, 19(12), 1949–1954. https://doi.org/10.1128/cvi.00427-12

San, A., Gul, D., & Arihan, O. (2023). A Light To Our Darkness: Bioluminescence and Its Uses In Medical Research. East J Med, 28(1), 68–74. https://doi.org/10.5505/ejm.2023.59862

Schramm, S., & Dieter Weiß. (2024). BioluminescenceThe Vibrant Glow of Nature and its Chemical Mechanisms. ChemBioChem, 25(9). https://doi.org/10.1002/cbic.202400106

Xia, T., Cheng, X., Zhan, W., & Liang, G. (2021). Activity‐Based Luciferase‐Luciferin Bioluminescence System for Bioimaging Applications. Analysis & Sensing, 1(4), 138–147. https://doi.org/10.1002/anse.202100035

Yang, Z., Zhu, Y., Dong, Z., Hao, Y., Wang, C., Li, Q., Wu, Y., Feng, L., & Liu, Z. (2022). Engineering bioluminescent bacteria to boost photodynamic therapy and systemic anti-tumor immunity for synergistic cancer treatment. Biomaterials, 281, 121332. https://doi.org/10.1016/j.biomaterials.2021.121332

Yuan, Z., Jiang, Q., & Liang, G. (2024). Inspired by nature: Bioluminescent systems for bioimaging applications. Talanta, 281, 126821. https://doi.org/10.1016/j.talanta.2024.126821


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