Aggregable gold nanoparticles for cancer photothermal therapy

Photothermal therapy (PTT) is an important non-invasive cancer treatment method. Enhancing the photothermal conversion efficiency (PCE) of photothermal agents (PTAs) and prolonging their tumor accumulation and retention are effective strategies to enhance the efficiency of cancer PTT. Recently, tremendous progress has been made in developing stimuli-responsive aggregable gold nanoparticles as effective PTAs for PTT. In this review, we discuss the chemical principles underlying gold nanoparticle aggregation and highlight the progress in gold nanoparticle aggregation triggered by different stimuli, especially tumor microenvironment-related factors, for cancer PTT. Covalent condensation reactions, click cycloaddition reactions, chelation reactions, and Au-S bonding, as well as non-covalent electrostatic interactions, hydrophobic interactions, hydrogen bonding, and van der Waals forces play key roles in the aggregation of gold nanoparticles. Enzymes, pH, reactive oxygen species, small molecules, salts, and light drive the occurrence of gold nanoparticle aggregation. Targeted aggregation of gold nanoparticles prolongs tumor accumulation and retention of PTAs and improves PCE, resulting in enhanced tumor PTT. Moreover, the major challenges of aggregable gold nanoparticles as PTAs are pointed out and the promising applications are also prospected at the end. With the deepening of research, we expect aggregable gold nanoparticles to become essential PTAs for tumor therapy.