Nanomedicine has emerged as a promising strategy to address some of the limitations of traditional modalities by combining nanotechnology, biology and medicine, especially in cancer research. Gold nanoparticles are among the most extensively used inorganic nanoparticles which benefit from high biocompatibility, flexible functionalization, strong and tunable resonant absorption, and production scalability. Moreover, their capability to enhance optical fields at their plasmon resonance enables high light absorption at low laser energies with the ability of converting this energy non-radiatively into heat, the so called Plasmonic Photothermal Therapy (PPTT). Recent developments reveal that flat cell culturing may induce misinterpretation due to its poor predictivity and reproducibility of real tumors when screening new therapies, and animal models lack of a human immune system apart from the ethical issues involving them. To try to overcome these limitations in the study of PPTT we stablished and optimized a simple 3D spheroid model using a renal carcinoma cell line to measure and compare the cellular uptake of gold nanorods of 11×40 nm size with two different surface chemistries, concentrations and incubation time. Furthermore, we performed a heating study with the most efficient uptake condition and carried out an evaluation of the induced cell death mechanism in our 3D spheroid system. results were compared with previous work using the same gold nanorods, laser power and irradiation time in 2D and in vivo systems to validate the potential of 3D models as a valuable tool for the application and further development of hyperthermia in cancer research.
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