In 2014, as part of an initiative to encourage my biochemistry students to actively read and discuss scientific journals and publications, I read a brief IEEE Spectrum article on the proposed use of graphene-based plasmon lasers (spasers) as a possible cancer therapeutic (1). The class blog entry was a popular topic for some time (2). Since that initial post, I made the decision to become a full-time medical writer, I had a family, and years had passed. When reviewing old course materials, I came across the post, and I decided that it would be interesting to do a follow-up review of this topic…sort of a “Spasers: Where are they now?“
Site-directed chemotherapy is highly desirable since healthy cells are also often affected by the treatment of malignant cells in systemic chemotherapeutics, resulting in general tissue destruction. The original article proposal was to develop a site-directed tumor therapy using a combination of lasers, nanotubes, antibodies, and surface plasmon technology. [For a brief tutorial on how surface plasmon resonance is used in small molecule interactions, please see the video by BiosensingUSA (3).] Spasers are similar to lasers except that surface plasmons are used in lieu of light. The original article hypothesizes that spasers could be used in the treatment of cancer. Carbon nanotubes conjugated to tumor-specific antibodies would be directed to the surface of the cancer cell where the surface plasmons are located. Then, a laser is used to excite the carbon nanotubes that then excite the surface plasmon. By exciting the surface plasmon, heat is generated. This heat then kills only the localized cancerous tissue in theory. The wavelength of light used in the laser is such that it can penetrate the skin and various layers to reach the cancerous tissues (1).
In a 2017 study by Galanzha and colleagues published in Nature Communications, the authors report developing a biocompatible spaser capable of generating stimulated emission inside either cells or animal tissues. The authors report detecting emission through approximately 1-mm-thick blood layer. This depth is more than 10-times greater than the depth typically observed using a conventional quantum dot method (4).
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One limitation to the use of spasers in vivo is the weak fluorescence signal due to the background noise (autofluorescence background found within tissues)(5-7). Harrington et al., 2019 (7) published results of a proof-of-concept experiment to create a ‘multimodal photoswitchable spaser’ utilizing a spherical plasmonic gold core with a non-absorbing polymer shell containing photoswitchable fluorescent proteins (PFPs). The researchers successfully synthesized stable spaser nanoparticles capable of photoswitching between wavelengths. The importance of these findings is the possible extension in spaser applications due to multicolor capacity while retaining photothermal applications. The authors conclude that “these results suggest that multimodal photoswitchable spasers could extend the traditional applications of spasers and PFPs in laser spectroscopy, multicolor cytometry, and theranostics with the potential to track, identify, and kill abnormal cells in circulation (7).”
References
- Tiny Cancer-Killing Death Rays: Spaser Therapy Proposed. IEEE Spectrum. Published November 4, 2014. Accessed July 1, 2022. https://spectrum.ieee.org/spaserpowered-cancer-therapy
- Star trek meets cancer therapy. MaestroSci. Accessed July 1, 2022. https://maestrosci.blogspot.com/2014/11/star-trek-meets-cancer-therapy.html
- Surface Plasmon Resonance Explained. Accessed July 1, 2022. https://www.youtube.com/watch?v=sM-VI3alvAI
- Galanzha EI, Weingold R, Nedosekin DA, et al. Spaser as a biological probe. Nat Commun. 2017;8:15528. doi:10.1038/ncomms15528
- Bindels DS, Goedhart J, Hink MA, van Weeren L, Joosen L, Gadella TWJ. Optimization of fluorescent proteins. Methods Mol Biol. 2014;1076:371-417. doi:10.1007/978-1-62703-649-8_16
- Yashchenok AM, Jose J, Trochet P, Sukhorukov GB, Gorin DA. Multifunctional polyelectrolyte microcapsules as a contrast agent for photoacoustic imaging in blood. J Biophotonics. 2016;9(8):792-799. doi:10.1002/jbio.201500293
- Harrington WN, Novoselova MV, Bratashov DN, et al. Photoswitchable spasers with a plasmonic core and photoswitchable fluorescent proteins. Sci Rep. 2019;9(1):12439. doi:10.1038/s41598-019-48335-6