Multiscale Thermal Analysis of Gold Nanostars in 3D Tumor Spheroids: Integrating Cellular-Level Photothermal Effects and Nanothermometry via X-Ray Spectroscopy.

In the pursuit of enhancing cancer treatment efficacy while minimizing side effects, near-infrared (NIR) photothermal therapy (PTT) has emerged as a promising approach. By using photothermally active nanomaterials, PTT enables localized hyperthermia, effectively eliminating cancer cells with minimal invasiveness and toxicity. Among these nanomaterials, gold nanostars (AuNS) stand out due to their tunable plasmon resonance and efficient light absorption. This study addresses the challenge of measuring nanoscale temperatures during AuNS-mediated PTT by employing X-ray absorption spectroscopy (XAS) within 3D tumor spheroids. It also aims to investigate the heat generated at the nanoscale and the resultant biological damage observed at a larger scale, utilizing confocal microscopy to establish connections between AuNS heat generation, tissue damage, and their impacts on cellular structure. These nanoscale and microscale thermal effects have been compared with macroscopic values obtained from infrared thermography, as part of a multiscale thermal analysis. The findings underscore the efficacy of AuNS in enhancing PTT and provide insights into the spatial distribution of thermal effects within tumor tissues. This research advances the understanding of localized hyperthermia in cancer therapy and underscores the potential of AuNS-based PTT for clinical applications.