posted on 2023-12-07, 11:45authored bySamir V. Jenkins, Seunghyun Jung, Azemat Jamshidi-Parsian, Michael J. Borrelli, Ruud P.M. Dings, Robert J. Griffin
Gold nanomaterials have been shown to augment radiation
therapy
both in vitro and in vivo. However, studies on these materials are
mostly phenomenological due to nanoparticle heterogeneity and the
complexity of biological systems. Even accurate quantification of
the particle dose still results in bulk average biases; the effect
on individual cells is not measured but rather the effect on the overall
population. To perform quantitative nanobiology, we coated glass coverslips
uniformly at varying densities with Au nanoparticle preparations with
different morphologies (45 nm cages, 25 nm spheres, and 30 nm rods).
Consequently, the effect of a specific number of particles per unit
area in contact with breast cancer cells growing on the coated surfaces
was ascertained. Gold nanocages showed the highest degree of radiosensitization
on a per particle basis, followed by gold nanospheres and gold nanorods,
respectively. All three materials showed little cytotoxic effect at
0 Gy, but clonogenic survival decreased proportionally with the radiation
dose and particle coverage density. A similar trend was seen in vivo
in the combined treatment antitumor response in 4T1 tumor-bearing
animals. The presence of gold affected the type and quantity of reactive
oxygen species generated, specifically superoxide and hydroxyl radicals,
and the concentration of nanocages correlated with the development
of more numerous double-stranded DNA breaks and increased protein
oxidation as measured by carbonylation. This work demonstrates the
dependence on morphology and concentration of radiation enhancement
by gold nanomaterials and may lead to a novel method to differentiate
intra- and extracellular functionalities of gold nanomedicine treatment
strategies. It further provides insights that can guide the rational
development of gold nanomaterial-based radiosensitizers for clinical
use.