Nanomaterials are a rapidly growing field of study in biomedicine, in part due to their multimodal functionality and in part due to their capacity for highly localized therapeutic effects. Two clinically used local treatments, laser thermal ablation and radiotherapy, can both be augmented through the use of Au nanomaterials, although the true mechanisms of action remain elusive. Many studies on these materials are extremely phenomenological due to the complexity of biological systems and the challenges associated with accurate quantification. Even accurate quantification still results in bulk average biases, i.e. the effect on individual cells is not measured, but rather the effect on the population. This uncertainty is confounded by variations among cell types and experimental parameters. Toward the goal of performing quantitative nanobiology, glass coverslips were uniformly coated with Au nanoparticles at different coverage densities. This allowed the effect of an accurate number of particles per unit area of the cell membrane to be ascertained. Photothermal-inducing laser treatment (10 min) was performed on cells growing on these surfaces, and much greater cell killing occurred than would be anticipated based on bulk temperature changes (&lt;42 °C). Theoretical modeling was used to determine the thermal gradient to more accurately define these results. Additionally, cells growing on these surfaces were treated with ionizing radiation and the radiosensitization as a function of the particle coverage density was determined. The surfaces were also coated with increasingly thick polymer layers prior to cell seeding to experimentally determine the distance dependence of the radiosensitization and whether the electrons generated from the surface of the particle were primarily acting on the cell membrane, the cell nucleus, or both. This platform has been tested initially using only Au nanocages without any active molecules, but ultimately drug loading, surface modification, morphology, and material changes will be performed to develop a more comprehensive understanding of the mechanisms of action at the nanotechnology/biology interface.

Nanoparticle-coated surfaces provide quantifiable insight into thermal and radiation effects

255th National Meeting (2018)

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