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Strong Electric Coupling at Nanoscale Interfaces in Combination with Ionizing Radiation Enables Synergistic Therapeutic Enhancement

K Cheng*, M Sano , C Jenkins , W Zhao , D Vernekohl , G Zhang , L Xing , Stanford Univ, School of Medicine, Stanford, CA


(Sunday, 7/29/2018) 4:00 PM - 5:00 PM

Room: Exhibit Hall | Forum 2

Purpose: Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide (TiO2), as a radio-sensitizer for radiation therapy of triple negative breast cancer (TNBC).

Methods: The synergistic enhancement of radiation sensitization via the interface between Au and TiO2components within an anisotropic nanostructure was investigated in vitro and in vivo. We measured intracellular reactive oxygen species (ROS) generation in TNBC cells (SUM159) and evaluated the antitumor effect of Au-TiO2 NPs in SUM159-tumor bearing mice. Antitumor effect of X-ray triggered Au-TiO2 NPs was evaluated in SUM159-tumor bearing mice.

Results: In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DATs uptake for a radio-sensitized radiation therapy.

Conclusion: We have demonstrated that a significantly enhanced radio-sensitization effect exists with dumbbell-like Au-TiO2 NPs on tumor tissues, even at relatively low concentrations. This could be beneficial in reducing radiation side effects to surrounding healthy tissues by lowering the dose to sufficiently treat a given tumor volume. Such tumoricidal effect works synergistically and provide a new opportunity for cancer therapy with excellent outcome.


Not Applicable / None Entered.


TH- Small Animal RT: Development (new technology and techniques)

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