Drug-loaded indocyanine green J-aggregates activate metalloimmunotherapy for sustained photothermal therapy of hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC) poses a significant therapeutic challenge, driving the need for novel treatment strategies. This study investigates the combination of photothermal therapy (PTT) and metalloimmunotherapy for HCC treatment using Co + diABZI@J-dICG nanoparticles. Indocyanine green (ICG), an FDA-approved near-infrared (NIR) dye, is dimerized into J-aggregates to enhance PTT by improving light absorption and photothermal efficiency. The cGAS-STING pathway, a key mediator of innate immunity, is activated by the STING agonist diABZI, while cobalt ions (Co²⁺) further enhance immune responses. The Co + diABZI@J-dICG nanoparticles take advantage of ICG's hepatotropic properties for sustained tumor accumulation and immune activation, resulting in significant tumor growth inhibition and reduced HCC recurrence following hepatectomy.