Acid-driven aggregation of selenol-functionalized zwitterionic gold nanoparticles improves the photothermal treatment efficacy of tumors

Improving nanomedicines' drug delivery efficiency and tumor penetration is of great significance for clinical cancer therapies. Although smart gold nanoparticles (Au NPs) with dynamic sizes can effectively cope with complex biological systems, the development of Au NPs with high stability and sensitivity between dispersion and aggregation still faces great challenges. Herein, we achieved an acid-driven aggregation of selenol-functionalized zwitterionic Au NPs (Au-Se-C-4-N-6) for promoting tumor targeting and improving photothermal treatment (PTT). During the blood circulation process in vivo, the Au-Se-C-4-N-6 exhibits better stability and strong anti-interference against biothiols. The dispersed Au-Se-C-4-N-6 can infiltrate deeply into the tumor region, and quickly assemble into large-size aggregates within the acidic tumor microenvironment (TME) to ensure higher tumor accumulation and retention. Simultaneously, the absorption band of the aggregated Au-Se-C-4-N-6 in the near-infrared (NIR) region was greatly increased, and the NIR laser irradiation of the aggregates resulted in a dramatic temperature increase to destroy cancer cells both in vitro and in vivo, which effectively enhances PTT with minimal side effects. These results confirm that pH-triggered size switching of selenol-functionalized Au NPs is a viable strategy for improving nanomedicines' stability, penetration and therapeutic efficacy.