Development of SERS Nanotag Using Anisotropic Gold Nanoparticles and AMP Polymers for Better Stability, Cell Uptake, and Signal Enhancement

Surface-Enhanced Raman Spectroscopy (SERS) has many advantages compared to other imaging techniques for better detection. SERS nanotags are often needed for greater signal enhancement, whose optimal performance relies on the metal nanoparticles core and coating. Anisotropic gold nanoparticles are the favorable choice due to its superiority compared to the other types. However, there are lack of researches about how these shapes affect its performance to the cells, which will be useful for its application in biomedical field such as cancer detection and photothermal therapy. Moreover, stability of the nanotags is still a major issue, especially in long term application such as during storage and shipping. Gold nanorods and gold nanotriangles were synthesized through chemical reduction as the anisotropic gold nanoparticles core, while gold nanospheres which were also synthesized through chemical reduction were used as a control against the other two nanoparticles. Mercaptoundecanoic acid (MUA), dihydrolipoic acid (DHLA), and polyethylene glycol (PEG) were used to synthesize alkylmercaptan-PEG (AMP) polymers through esterification as the protective coating. UV-Vis spectroscopy, Dynamic Light Scattering, zeta potential measurement, and Transmission Electron Microscope imaging were performed for characterizations. Nuclear Magnetic Resonance imaging was performed to ensure a successful esterification. Gold nanoparticles, AMP polymers, and Raman reporters will be mixed together to create SERS nanotags. The effectiveness of AMP polymers in maintaining the nanotags’ stability under lyophilization, the effect of different nanoparticle shapes in the cellular uptake, and the signals generated from different nanoparticle shapes was explored. All gold nanoparticles were synthesized successfully, while MUA-PEG and DHLA-PEG were synthesized as the AMP polymers. PEGylated gold nanospheres seemingly aggregated after lyophilization, but had the UV-Vis spectrum return to pre-lyophilization condition after brief sonication. All gold nanoparticles were internalized by A549 cells after 3-hour incubation, in which gold nanorods were taken the fastest, followed by gold nanotriangles and gold nanospheres respectively. All gold nanoparticles generated weak but noticeable Raman signal of DTTC iodide dye; in particular order gold nanorods had the strongest signal, followed by gold nanotriangles, and gold nanospheres had the weakest signal. It can be concluded that gold nanorods and gold nanotriangles showed promise for further use, with more trials needed to unlock more potentials of the SERS nanotags.