Iodine-starch chromogenic nanoplatforms for photothermal precision and IDO-mediated colorectal cancer therapy

Colorectal cancer (CRC) remains a significant global health challenge, as current treatments such as surgery and chemotherapy are limited by poor precision, severe side effects, and the complex tumor microenvironment. Photothermal therapy (PTT) offers a promising alternative; however, conventional photothermal agents largely rely on synthetic materials, raising concerns about stability, toxicity, and metabolic degradation. To overcome these limitations, this study aimed to develop a biocompatible photothermal nanoplatform using iodine (I₂)-loaded acetylated starch nanoparticles (ASt NPs). The helical structure of ASt efficiently encapsulated I₂, facilitating a chromogenic interaction that provides near-infrared (NIR) absorbance and enables the NPs to function as intrinsic photothermal agents for PTT. Under NIR irradiation, these NPs generated localized heating, enabling precise temperature modulation through reversible color changes. The ASt NPs also encapsulated the IDO1 inhibitor NLG919 (IN@ASt NPs), enhancing immune modulation by downregulating IDO1 expression and reducing PTT-induced immunosuppression. This synergy induced immunogenic cell death, activated strong antitumor immunity, and inhibited lung metastasis in CRC models. Thus, this innovative platform leverages the biocompatibility of carbohydrate-based materials to address key challenges in CRC therapy.