Light-initiated aggregation of gold nanoparticles for synergistic chemo-photothermal tumor therapy

Abstract

The combination of chemotherapy with photothermal therapy (PTT) has attracted extensive attention due to its excellent synergetic effect attributing to the fact that hyperthermia can effectively promote the tumor uptake of chemotherapeutic drugs. Herein, we propose a light-initiated gold nanoparticle (AuNP) aggregation boosting the uptake of chemotherapeutic drugs for enhanced chemo-photothermal tumor therapy. Novel light-responsive AuNPs (tm-AuNPs) were rationally designed and fabricated by conjugating both 2,5-diphenyltetrazole (Tz) and methacrylic acid (Ma) onto the surface of AuNPs with small size (∼20 nm). Upon the irradiation of 405 nm laser, AuNPs could be initiated to form aggregates specifically within tumors through the covalent cycloaddition reaction between Tz and Ma. Taking advantage of the controllable photothermal effect of Au aggregates under NIR excitation, improved enrichment of doxorubicin (DOX) in tumor tissues was realized, combined with PTT, resulting in outstanding synergetic anti-tumor efficacy in living mice. We thus believe that this light-initiated AuNP aggregation approach would offer a valuable and powerful tool for precisely synergistic chemo-photothermal tumor therapy.