Fabrication of nanoparticles with precisely controllable plasmonic properties as tools for biomedical applications†

Metal nanoparticles are established tools for biomedical applications due to their unique optical properties, primarily attributed to localized surface plasmon resonances. They show distinct optical characteristics, such as high extinction cross-sections and resonances at specific wavelengths, which are tunable across the wavelength spectrum by modifying the nanoparticle geometry. These attributes make metal nanoparticles highly valuable for sensing and imaging in biology and medicine. However, their widespread adoption is hindered due to challenges in consistent and accurate nanoparticle fabrication and functionality as well as due to nanotoxicological concerns, including cell damage, DNA damage, and unregulated cell signaling. In this study, we present a fabrication approach using nanoimprint lithography in combination with thin film deposition which yields highly homogenous nanoparticles in size, shape and optical properties with standard deviations of the main geometry parameters of less than 5% batch-to-batch variation. The measured optical properties closely match performed simulations, indicating that pre-experimental modelling can effectively guide the design of nanoparticles with tailored optical properties. Our approach also enables nanoparticle transfer to solution. Particularly, we show that the surface coating with a PEG polymer shell ensures stable dispersions in buffer solutions and complex cell media for at least 7 days. Furthermore, our in vitro experiments demonstrate that these nanoparticles are internalized by cells via endocytosis, exhibit good biocompatibility, and show minor cytotoxicity, as evidenced by high cell viability. In the future, our high-precision nanoparticle fabrication method together with tunable surface plasmon resonance and reduced nanotoxicity will offer the possibility to replace conventional nanomaterials for biomedical applications that make use of an optical response at precise wavelengths. This includes the use of the nanoparticles as contrast agents for imaging, as probes for targeted photothermal cancer therapy, as carriers for controlled drug delivery, or as probes for sensing applications based on optical detection principles.