Innovative Approaches to Cancer Biomarker Detection

Unfortunately, cancer is still one of the largest obstacles in contemporary medicine, and early detection can help increase patients’ survival rates. Since its inception, the concept of cancer biomarkers, or biological markers for cancer diagnosis, has been widely embraced due to its recommendations in the identification of the disease, the development of a treatment plan, and the evaluation of the progress achieved in treatment. The methods of biomarker detection that have been used in the past are satisfactory, but they have drawbacks such as low sensitivity and invasiveness. To these, some solutions have been developed that employ some of today’s enhanced features, such as nanotechnology, biosensing, and molecular biology, among others. These advanced methods have the potential to greatly improve the discovery of biomarkers for cancer diagnosis, prognosis, and treatment due to their non-invasive nature and increased sensitivity or specificity, thus helping to bring about more individualized cancer care.

The Role of Nanotechnology in Biomarker Detection

Nanotechnology has brought new possibilities for the identification of cancer biomarkers and tools working on the molecular and cellular levels. Some of the advancements in this area include the application of nanoparticles, which can be compounded in such a way that they detect biomarkers related to cancer cells with high sensitivity. Among all the noble metal NPs, gold and silver have been studied more because they possess optical characteristics. Nanoparticles that can be conjugated with antibodies or aptamers that selectively interact with biomarker molecules for detection by changes in fluorescence, electrochemical, or color changes can be used.

For instance, modern advancements have revealed new applications of decahedral silver nanoparticles in fluorescence polarization-based detection methods. These nanoparticles can offer enzyme-free, highly sensitive, and specific miRNA capture with specific miRNAs like miRNA-21, which has been associated with several cancers. Due to these properties of the nanoparticles as well as strand displacement reactions, the proposed method is capable of detecting low levels of miRNAs in biological samples and is invasive while being highly specific.

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Fluorescence-Based Biosensing for Cancer Biomarkers

Fluorescence biosensing has become one of the most efficient methods of cancer biomarker detection due to its high sensitivity and the possibility of analyzing biomarkers in complicated biological samples. Another comprehensible method based on the use of aptamers includes the application of fluorescence polarization assays. Aptamers are small oligonucleotides, which can be DNA and/or RNA, that can selectively and with high affinity engage target molecules. The researchers have used fluorescently tagged aptamers to detect the actual amount of exosomes, which are the extracellular vesicles that transport cancer biomarkers.

Proteins, lipids, and nucleic acids make up the biomolecules that are present in the exosome, which is why they hold vast potential for cancer diagnosis. Fluorescence polarization can be employed to detect and quantify exosomes, providing a non-invasive, reproducible, and highly sensitive system for the detection of cancer biomarkers that can be translated to routine clinical use.

Another fluorescence-based method includes the construction of time-resolved fluorescence, which has been advanced to form FLIM, fluorescence lifetime imaging microscopy that determines the time a molecule takes in the excited state before it emits a fluorescence. This technique has been modified for cancer biomarkers using fluorescently labeled probes that have a preference for particular biomarkers. FLIM is advantageous for detecting biomarkers at low concentrations and in real-time, making it useful in early cancer diagnosis.

Quantum Dots: A New Frontier in Biosensing

Another modern technique that can be used in the detection of biomarkers for cancer is quantum dots (QDs). These semiconductor nanoparticles have some peculiar characteristics: the dependence of the emitted light wavelength on the size of the nanoparticles and their high photostability, which makes them suitable for application in biosensors. The most emerging research activities in the area of QD bio-sensing have been directed to the analysis of numerous types of cancer biomarkers, such as proteins, nucleic acids, and small molecules.

For example, quantum dots have been used in biosensors to detect miRNA-21. Here, the quantum dots can funnel a bright fluorescent signal upon binding to the target biomarker. This way, not only does the sensitivity of the detection increase, but various biomarkers can be detected at the same time by employing quantum dots of various sizes and fluorescence wavelengths. The ability to multiplex in quantum dots makes it desirable for cancer diagnostics, in which simultaneous determination of multiple biomarkers of the disease is typically needed.

Smartphone-Integrated Diagnostic Tools

The integration of biosensing technologies with smartphones represents a significant step forward in the development of portable and user-friendly diagnostic tools. Smartphones offer a powerful platform for data acquisition, processing, and communication, making them ideal for use in point-of-care testing. Recent innovations have led to the development of smartphone-integrated systems for the detection of cancer biomarkers, utilizing microfluidic devices and nucleic acid amplification techniques.

One such example is a mobile platform that uses loop-mediated isothermal amplification (LAMP) combined with microfluidics and smartphone detection for the multiplexed detection of disease-specific nucleic acid sequences. This platform enables the detection of multiple cancer biomarkers simultaneously, providing a rapid and cost-effective diagnostic tool that can be used outside of traditional laboratory settings. The portability and ease of use of smartphone-integrated diagnostic tools have the potential to greatly expand access to cancer diagnostics, particularly in resource-limited settings.

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Metal-Enhanced Fluorescence for Cancer Biomarker Detection

The general incorporation of biosensing systems with smartphones has been a major advancement in the production of portable and easy-to-use diagnostic devices. Mobile phones, especially the smart ones, are perfect tools for data collection, analysis, and sharing and are therefore suitable for point-of-care testing. The advancements of the last few years have brought in smartphone-associated systems for the identification of cancer biomarkers using microfluidic tools, along with nucleic acid amplification tests.

An example of this is a portable cell for the LAMP multiplex analysis of the presence of disease-associated nucleic acid sequences equipped with microfluidics and a smartphone reader. This offers the potential to identify several cancer biomarkers at once, thus allowing the creation of a quick and inexpensive diagnostic tool that can be implemented in a non-hospital environment. Smartphone-integrated diagnostic tools are portable and simple to use; they might significantly increase the accessibility of cancer diagnostics, especially in LMICs.

Aptamers and Their Role in Biomarker Detection

Another technique that has been considered for cancer biomarker detection is called metal-enhanced fluorescence (MEF). MEF incorporates the application of metallic nanostructures for amplification of the fluorescence signal from the fluorophores, thereby increasing the limit of sensitivity. All optically, some biosensors employ silver-enhanced fluorescence polarization (BioSEF) for the rapid detection of protein biomarkers such as lactoferrin, which has a relationship with cancer.

Due to their high selectivity, conventional and modified aptamers can target various kinds of biomarkers, such as nucleic acids, proteins, and exosomes. Non-antibody-binding molecules, such as aptamers, have some advantages over conventional molecular recognition elements, like antibodies; they are cheaper, synthesizable, and amendable for optimization. Continuous advancement in aptamer-based bio sensitization is expected to result in new diagnostic tests with increased specificity for identifying cancer biomarkers.

Conclusion

It is seen that the possibilities for the early and accurate detection of cancer biomarkers have expanded, and new methods appear constantly. None of these has limited scientists and engineers from envisioning and developing superior tools like nanotechnology, fluorescence-based biosensing, quantum dots, smartphone-integrated tools, metal-enhanced fluorescence, and aptamers, among others. Such developments have the possibility of altering the diagnostic techniques for cancer and making them more efficient, painless, and accurate. Therefore, as future research comes through, these innovative approaches will be intensified and adopted in clinical practice, thereby enhancing the global outcome of cancer patients.

References

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2. Rupsa Datta, Tiffany M. Heaster, Joe T. Sharick, Amani A. Gillette, and Melissa C. Skala. Fluorescence lifetime imaging microscopy: fundamentals and advances in instrumentation, analysis, and applications. Journal of Biomedical Optics 25(7), 071203 (13 May 2020).

3. Ma, F., Li, C.C. and Zhang, C.Y., 2018. Development of quantum dot-based biosensors: principles and applicationsJournal of Materials Chemistry B6(39), pp.6173-6190.

4. Chen W, Yu H, Sun F, Ornob A, Brisbin R, Ganguli A, Vemuri V, Strzebonski P, Cui G, Allen KJ, Desai SA, Lin W, Nash DM, Hirschberg DL, Brooks I, Bashir R, Cunningham BT. Mobile Platform for Multiplexed Detection and Differentiation of Disease-Specific Nucleic Acid Sequences, Using Microfluidic Loop-Mediated Isothermal Amplification and Smartphone Detection. Anal Chem. 2017 Nov 7;89(21):11219-11226. doi: 10.1021/acs.analchem.7b02478. Epub 2017 Sep 5. PMID: 28819973.

5. Chen Z, Li H, Jia W, Liu X, Li Z, Wen F, Zheng N, Jiang J, Xu D. Bivalent Aptasensor Based on Silver-Enhanced Fluorescence Polarization for Rapid Detection of Lactoferrin in Milk. Anal Chem. 2017 Jun 6;89(11):5900-5908. doi: 10.1021/acs.analchem.7b00261. Epub 2017 May 12. PMID: 28467701.

6. Gil HM, Price TW, Chelani K, Bouillard JG, Calaminus SDJ, Stasiuk GJ. NIR-quantum dots in biomedical imaging and their future. iScience. 2021 Feb 15;24(3):102189. doi: 10.1016/j.isci.2021.102189. PMID: 33718839; PMCID: PMC7921844.

7. Klębowski B, Depciuch J, Parlińska-Wojtan M, Baran J. Applications of Noble Metal-Based Nanoparticles in Medicine. Int J Mol Sci. 2018 Dec 13;19(12):4031. doi: 10.3390/ijms19124031. PMID: 30551592; PMCID: PMC6320918.

8. Li, X., Ding, X., Li, Y., Wang, L. and Fan, J., 2016. A TiS 2 nanosheet enhanced fluorescence polarization biosensor for ultra-sensitive detection of biomoleculesNanoscale8(18), pp.9852-9860.

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