3D cultures for modeling nanomaterial-based photothermal therapy

Photothermal therapy (PTT) is one of the most promising techniques for cancer tumor ablation. Nanoparticles are increasingly being investigated for use with PTT and can serve as theranostic agents. Based on the ability of near-infrared nano-photo-absorbers to generate heat under laser irradiation, PTT could prove advantageous in certain situations over more classical cancer therapies. To analyze the efficacy of nanoparticle-based PTT, preclinical in vitro studies typically use 2D cultures, but this method cannot completely mimic the complex tumor organization, bioactivity, and physiology that all control the complex penetration depth, biodistribution, and tissue diffusion parameters of nanomaterials in vivo. To fill this knowledge gap, 3D culture systems have been explored for PTT analysis. These models provide more realistic microenvironments that allow spatiotemporal oxygen gradients and cancer cell adaptations to be considered. This review highlights the work that has been done to advance 3D models for cancer microenvironment modeling, specifically in the context of advanced, functionalized nanoparticle-directed PTT.