The combination of biological variation and nanomaterial heterogeneity makes elucidating the mechanisms of interactions between cells and nanoparticles extremely complicated. Accurate nanoparticle quantification can be extremely challenging, and cellular response can change based on the location of the nanoparticle and the cell type under investigation. These complications are only amplified by the addition of external stimuli. These limitations have yielded a wide range of studies that show effects, but often provide little mechanistic insight. Gold (Au) nanomaterials were stably immobilized onto glass coverslips treated with mercaptosilane to control both the average number of nanoparticles that interact with cells and their spatial orientation relative to the cell membrane. Surfaces were characterized optically and by electron microscopy to confirm their surface density and uniformity. The thermal response of Au nanocage-coated surfaces to near infrared laser irradiation was measured in cell culture medium and modeled computationally. The modeling showed a vastly higher thermal dose than would be predicted by bulk temperature measurements. Adherent or non-adherent cell lines were cultured directly on the nanocage-coated surface or in the medium, respectively, in culture wells and laser irradiation was applied. Survival of cells growing in suspension correlated with the bulk temperature increase in the culture medium, as measured by viability assay. Conversely, adherent cells exhibited a much greater susceptibility than expected from the bulk temperature measurement, which is ostensibly related to the close interaction with the nanoparticles on their growth substrate and induction of substantially greater thermal dose upon laser exposure. This platform is designed to be a new tool to determine how many particles need to be in contact with a cell to induce desired physical or biological effects. Here we demonstrate the delivery of precise thermal doses following laser irradiation. The anticipated biological effects based on bulk measurements vastly underestimated the effects that were observed, which is ascribed to the proximity of the nanoparticle to the cell and the extraordinary high surface temperature of the particle. This platform could be expanded to a variety of nanoparticles, external stimuli, and cell types to enable more deliberate and optimized application of nanomedicine.
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The authors thank J. Chen for providing facilities for AuNC synthesis, P. Corry, N. Koonce, and J. Bischof for helpful discussion.
Funding for this work was provided by National Science Foundation EPSCoR RIII Award 1457888 and the Translational Research Institute grant TL1 TR003109 through the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH).
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Jenkins, S.V., Jung, S., Shah, S. et al. Nanoscale investigation and control of photothermal action of gold nanostructure-coated surfaces. J Mater Sci 56, 10249–10263 (2021). https://doi.org/10.1007/s10853-021-05947-6