Acid-Triggered in Situ Aggregation of Gold Nanoparticles for Multimodal Tumor Imaging and Photothermal Therapy

Photothermal agents with high photothermal transfer efficiencies in the near-infrared (NIR) region are important for enhanced photothermal therapy (PTT) of tumors. Herein, we developed a strategy for the acid-triggered in situ aggregation of a system based on peptide-conjugated gold nanoparticles (GNPs). In an acidic environment, the GNPs formed large aggregates in solution, in cell lysates, and in tumor tissues, as observed by transmission electron microscopy (TEM). As a consequence of the aggregation, their UV–vis absorbance in the NIR region was greatly increased, and laser irradiation of the GNPs resulted in a dramatic increase in the temperatures of solutions and tumors that contained the GNP system. When exposed to NIR irradiation, the aggregates formed by the GNP system under acidic conditions were capable of producing a sufficient level of hyperthermia to destroy cancer cells both in vitro and in vivo. Interestingly, the GNP aggregates showed enhanced properties in multiple imaging modalities, including computed tomography (CT), photoacoustic (PA), and photothermal (PT) imaging. Thus, we have developed a novel probe for enhanced multimodal tumor imaging. These findings prove that a strategy involving the acid-triggered in situ aggregation of a GNP system can increase the photothermal transfer efficiency for low to high energy conversion, thus boosting the therapeutic specificity and antitumor efficacy of PTT and facilitating multimodal imaging.