Double safety guarantees: Food-grade photothermal complex with a pH-triggered NIR absorption from zero to one

Photothermal therapy has aroused great attention and showed promising potential in minimally invasive tumor ablation, but the clinical translation is still stifled by the concerns of unwanted injury to normal tissues. The safety concerns might be completely solved only when the two security obstacles of "material-toxicity" and "photo-toxicity" were overcome simultaneously. Herein, a completely non-toxic food-grade photothermal transduction agent (PTA) with double safety guarantees was invented, which shows an absolute transformation of the photothermal effect from "0" to "1" after being triggered by an acidic tumor microenvironment. Inspired by the classical starch-iodine test, a preprogrammed [starch-KI-KIO₃] complex was prepared in large quantities through a modified wet-milling procedure. It's demonstrated that a macroscopic consecutive reaction could be triggered by low pH to produce the starch-iodine complex which can generate lethal temperature under the near-infrared light irradiation. Meanwhile, the PTA shows excellent biocompatibility with no "material-toxicity" owing to the raw materials drawn from our daily food. Animal experiments reveal that the tumor microenvironment can activate the switch of photothermal effect from "0" to "1" successfully, which is thus responsible for the discriminative photo-damage to the tumor region while no "photo-toxicity" to normal tissue. The good treatment efficacy confirms the feasibility of such photothermal transduction agents with double safety guarantees in clinical applications.