Synthesis & Functionalization of Hybrid Plasmon-Semiconductor Nanoparticles for Cancer Phototherapy

Clinical modality based on light activation and photosensitizers, phototherapy, has been recognized as a novel alternative for cancer therapy owning to its high selectivity, safety and compatibility with other tumor ablation modalities. However, key challenges such as low light penetration, low generation rate of reactive oxygen species (ROS) for photodynamic therapy (PDT) or of heat for photothermal therapy (PTT), along with poor distribution specificity of photosensitizers have restricted its widespread clinical use, which requires rational design and improvement on photosensitizers. Herein we propose a strategy that combines plasmonic gold nanorods (AuNR), which can efficiently generate hot electrons under laser irradiation thanks to its localized surface plasmon resonance, with semiconductor materials such as TiO₂. The generated hot electrons can be injected into the conduction band of TiO₂ and eventually produce ROS (Hydroxyl radicals), radicals that will lead to cell apoptosis. By controlling the aspect ratio of AuNR, the longitudinal absorption of AuNR can be tuned from 700 to 1000 nm, a region where light gets an optimal penetration into the tissue. We characterized the production of hydroxyl radicals by AuNR/TiO₂ nanoparticles under continuous wave or pulsed irradiation at 800 nm by measuring the degradation rate of methylene blue. Then we designed surface polymeric ligands based on polyethylene glycol to ensure the colloidal stability of these hybrid AuNR/TiO₂ nanoparticles in a physiological environment. Finally, these functionalized AuNR/TiO₂ nanoparticles were incubated with HeLa cells. We demonstrated that irradiation of these nanoparticles by a continuous 808 nm laser was effective to produce ROS and kill cancer cells, while incubation with nanoparticles in the absence of irradiation or irradiation in the absence of the nanoparticles did not modify the cell viability.