Photothermal Techniques for Cancer Diagnosis and Treatment

Photothermal spectroscopy (PTS) and photothermal therapy (PTT) are advanced techniques used in cancer diagnosis and treatment. PTS refers to a set of highly sensitive methods that detect thermal variations in materials when exposed to radiation, while PTT utilizes these principles to treat cancer by targeting tumors with heat.

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Unlike traditional spectrometric methods, which gather data based on the light a sample transmits, reflects, or emits, photothermal spectroscopy focuses on detecting the heat generated through non-radiative relaxation.¹

Over the past two decades, these methods have reached the sensitivity of single particles and single molecules, which has led to novel applications in material science and biology.²

In cancer diagnosis and treatment, PTS and PTT are recognized for their ability to enhance imaging and therapeutic precision.

Everything You Should Know About Photothermal Spectroscopy

Mechanisms of PTS in Cancer Detection

PTS works on the principle of converting absorbed optical energy into heat within a sample, causing changes in its properties like density or refractive index.¹ Several methods within PTS analyze these thermal changes, each with a distinct approach:

• Photoacoustic Spectroscopy (PAS): Detects acoustic waves generated by the sample when exposed to electromagnetic waves.³
• Photothermal Deflection Spectroscopy (PDS): Measures thermal changes by detecting laser beam deflection due to shifts in the sample’s refractive index.
• Thermal Lens Spectroscopy: Uses a temperature gradient formed by nonuniform Gaussian heating.
• Photothermal Radiometric Spectroscopy: Exposes the sample to continuous laser radiation.
• Photothermal Interferometric Spectroscopy: Measures heat changes by detecting phase shifts in light using an interferometer.¹

Each of these methods leverages photothermal conversion principles to reveal unique insights into the sample properties.

In cancer detection, PTS identifies cancerous cells at the molecular level by exploiting their unique optical absorption properties compared to healthy cells.⁴ PTS can differentiate cancerous cells with high sensitivity by detecting localized heating caused by these distinct absorption characteristics.

PAS can detect deeply embedded tumors by measuring temperature-induced changes in the photoacoustic signal, leveraging the optical contrast between cancerous and healthy tissue.⁵ The presence of photo absorbers in tumors increases the contrast, aiding in the identification of cancerous lesions.

Most importantly, PTS offers clear images of cancer cells with minimal background noise and can be used directly on samples without staining.²

Clinical Applications of PTS in Early Cancer Diagnosis

PTS has emerged as a promising technique for early cancer detection, as evidenced by several case studies.

In one study, researchers used photothermal infrared spectroscopy (PIRS) to distinguish between normal and metastatic oral cancer in cervical lymph nodes.⁶ This technique utilized specific infrared wavelengths, achieving accuracy comparable to the traditional methods like hematoxylin and eosin staining, the gold standard in pathology.

Another study utilized PIRS to distinguish between malignant and non-malignant lung cells, reaching classification accuracies close to 99 %.⁷ Nonlinear microscopic techniques based on PTS were also used to image mouse melanoma without staining, to produce high-contrast, high-resolution images superior to conventional optical microscopy.⁸

In another study, PAS was paired with machine learning to categorize three types of breast cancer (triple-negative) in laboratory research.⁹ They identified a specific molecule that could serve as a biomarker for these breast cancer types, showcasing the ability of these techniques to provide precise and early cancer detection.Top of Form

The clinical benefits of PTS are primarily because of its non-invasive nature and high precision. Unlike traditional diagnostic methods that may require staining or are prone to high background interference and complicated procedures, PTS offers a direct and accurate assessment of thermal changes at the molecular level.¹⁰ This method is especially useful because it can detect multiple biomarkers at once, helping identify and locate the cancerous cells.⁹

Additionally, nanoparticles with surface plasmon resonance (SPR) have been found to improve the imaging abilities of PTS-based methods in cancer diagnosis. The development of advanced photothermal nanomaterials and the availability of portable, cost-effective PTS equipment have expanded its clinical applications, making it a versatile and efficient diagnostic tool.

Photothermal Therapy for Cancer Treatment

Photothermal therapy (PTT) is a cutting-edge cancer treatment that utilizes electromagnetic radiation to target tumors with near-infrared irradiation. This technique is extremely precise, non-invasive, and effective, as it uses a high-intensity laser to target the tumor directly.

PTT employs photothermal agents with surface plasmon resonance (SPR) properties, such as carbon, gold, silver, and germanium nanoparticles. These agents efficiently convert light into heat, leading to localized photochemical, photomechanical, and photothermal reactions that selectively destroy cancer cells.¹¹

PTT has also been successful in treating breast cancer and melanoma. For instance, when used together with photothermal therapy, the compound hypericin enhances the production of reactive oxygen species needed for photodynamic therapy while also generating heat, achieving a photothermal conversion efficiency of 29.3 %.¹² This combination has proven effective in breast cancer treatment.

PTT can be utilized independently, guided by multimodal imaging, or in conjunction with other therapies, providing a highly specific and minimally invasive cancer treatment option.

Future Outlook

Emerging trends in PTS and PTT could revolutionize cancer diagnosis and therapy. One significant advancement is the integration of PTS with other modalities, such as photoacoustic and gene therapies, to address challenges like the precise control of biodistribution and clearance of photothermal agents.¹³ This multi-modal approach promises to enhance treatment effectiveness and specificity, potentially improving patient outcomes.

Mid-infrared photothermal microscopy is another technique that offers label-free imaging and enables detailed analysis of cellular components through their infrared fingerprints.¹⁴ Additionally, recent advancements in photothermal circular dichroism microscopy have facilitated the detection of minute circular dichroism signals in single chiral nano-objects, opening new avenues for studying chiral molecules in cancer cells.²

Despite its promise, PTT faces challenges, such as nanoparticle cytotoxicity and prolonged retention time.¹⁵ The development of advanced photothermal agents, such as modified gold nanoparticles and gold nanoshells, continues to show promise in PTT applications. These nanostructures are being improved to boost their ability to convert light into heat, precisely target specific cells, and reduce any potential harm to healthy cells.

These developments have led to the creation of photothermal nanotherapeutics, which have demonstrated efficacy in preclinical studies, particularly for treating metastatic cancers.¹⁶ Future research is focused on understanding the mechanisms of cell death induced by PTT to achieve better control over the system.

Furthermore, the evolution of wide-field photothermal microscopy, supported by modern ultrafast and lock-in cameras, is expected to broaden the scope of photothermal imaging.¹⁷ This technological advancement will likely accelerate the diagnostic process, making PTS and PTT more practical and accessible in clinical settings, thus enhancing their application in cancer diagnosis and treatment.

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References and Further Reading

1. Proskurnin, MA. (2014). Photothermal spectroscopy. In Laser spectroscopy for sensing. DOI: 10.1533/9780857098733.2.313
2. Adhikari, S., Spaeth, P., Kar, A., Baaske, MD., Khatua, S., Orrit, M. (2020). Photothermal microscopy: imaging the optical absorption of single nanoparticles and single molecules. ACS nano. DOI: 10.1021/acsnano.0c07638
3. West, GA., Barrett, JJ., Siebert, DR., Reddy, KV. (1983). Photoacoustic spectroscopy. Review of Scientific Instruments. DOI: 10.1063/1.1137483
4. Huang, X., El-Sayed, MA. (2010). Gold nanoparticles: Optical properties and implementations in cancer diagnosis and photothermal therapy. Journal of advanced research. DOI: 10.1016/j.jare.2010.02.002
5. Gonzalez, EA., Bell, MAL. (2023). Photoacoustic imaging and characterization of bone in medicine: overview, applications, and outlook. Annual Review of Biomedical Engineering. DOI: 10.1146/annurev-bioeng-081622-025405
6. Al Jedani, S., et al., (2024). An optical photothermal infrared investigation of lymph nodal metastases of oral squamous cell carcinoma. Scientific Reports. DOI: 10.1038/s41598-024-66977-z
7. He, J., Wang, N., Tsurui, H., Kato, M., Iida, M., Kobayashi, T. (2016). Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue. Scientific Reports. DOI: 10.1038/srep30209
8. He, J., Miyazaki, J., Wang, N., Tsurui, H., Kobayashi, T. (2015). Label-free imaging of melanoma with nonlinear photothermal microscopy. Optics letters. DOI: 10.1364/OL.40.001141
9. Li, J., Chen, Y., Ye, W., Zhang, M., Zhu, J., Zhi, W., & Cheng, Q. (2023). Molecular breast cancer subtype identification using photoacoustic spectral analysis and machine learning at the biomacromolecular level. Photoacoustics, 30. DOI: 10.1016/j.pacs.2023.100483, https://www.sciencedirect.com/science/article/pii/S2213597923000368
10. Wang, Z., Wang, M., Wang, X., Hao, Z., Han, S., Wang, T., Zhang, H. (2023). Photothermal-based nanomaterials and photothermal-sensing: An overview. Biosensors and Bioelectronics. DOI: 10.1016/j.bios.2022.114883
11. Zhi, D., Yang, T., O’hagan, J., Zhang, S., Donnelly, RF. (2020). Photothermal therapy. Journal of Controlled Release. DOI: 10.1016/j.jconrel.2020.06.032
12. Wu, JJ., et al. (2023). Hypericin: A natural anthraquinone as promising therapeutic agent. Phytomedicine. DOI: 10.1016/j.phymed.2023.154654
13. Tabish, TA., Dey, P., Mosca, S., Salimi, M., Palombo, F., Matousek, P., Stone, N. (2020). Smart gold nanostructures for light mediated cancer theranostics: combining optical diagnostics with photothermal therapy. Advanced Science. DOI: 10.1002/advs.201903441
14. Tamamitsu, M., et al. (2020). Label-free biochemical quantitative phase imaging with mid-infrared photothermal effect. Optica. DOI: 10.1364/OPTICA.390186
15. Hwang, S., Nam, J., Jung, S., Song, J., Doh, H., Kim, S. (2014). Gold nanoparticle-mediated photothermal therapy: current status and future perspective. Nanomedicine. DOI: 10.2217/nnm.14.147
16. Zou, L., et al. (2016). Current approaches of photothermal therapy in treating cancer metastasis with nanotherapeutics. Theranostics. DOI: 10.7150%2Fthno.14988
17. Kim, JD, et al. (2021). Wide-field photothermal reflectance spectroscopy for single nanoparticle absorption spectrum analysis. Nanophotonics. DOI: 10.1515/nanoph-2021-0203

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