Boosting Cancer Cell Uptake of Gold Nanoparticles by Light-Modulated Protein Corona Reorganization for Tumor Ablation

Nanoparticles (NPs) administered into the human body are spontaneously modified by forming a protein corona, which is crucial for their biological activity. While NP-based photothermal therapy is an established noninvasive modality for tumor ablation, the impact of light irradiation on protein corona formation and clinical outcomes is unclear. This study unveils the promotive role of light irradiation in cancer cell uptake of gold nanoparticles (GNPs) by modulating the GNP–protein and protein–protein interactions within the corona. Specifically, infrared light irradiation increases the local temperature around GNPs to induce partial unfolding of corona proteins, increasing the availability of binding sites and enhancing adsorption. Additionally, light intensifies competition among different proteins for adsorption, resulting in a 25% increase in the abundance of higher molecular weight proteins, such as human serum albumin (HSA), on the GNP surface after irradiation. Notably, GNPs with positively charged surfaces, compared to GNPs with other modifications, exhibit more significant changes in the protein corona due to stronger electrostatic interactions with proteins (1.32 ± 0.17 × 10 3 kJ/mol). These variations in the amount, structure, and composition of associated proteins result in a 14.26% increase in GNP uptake by cancer cells, likely due to modifications at the GNP–cell membrane interface. Our findings highlight the critical role of light irradiation in influencing protein corona dynamics and cellular interactions, suggesting its potential as a valuable engineering tool in nanomedicine.