Rational Design of NIR‐II Fluorescence/Photoacoustic Nanosensor Tailored for Mechanisms of Diabetes‐Related Breast Cancer

Abstract Breast cancer (BC) is the second most common cause of cancer induced death worldwide. Current statistics has disclosed that the diabetic BC patients have significantly worse survival rate compared with nondiabetic BC patients. However, the specific mechanism is still being explored. Herein, a novel NIR‐II nanosensor DNPS for nitric oxide (NO) with fluorescence/photoacoustic (FL/PA) imaging capability is developed to explore the mechanism by which diabetes promoting breast cancer progression. In diabetic BC model, DNPS exhibits great advantages of low intrinsic background, high sensitivity, and deep tissue penetration and successfully confirmed the expression level of NO is higher than BC model, indicating that diabetes causes elevated nitric oxide levels in the tumor microenvironment. RNA‐seq analysis results show that hyperglycemia caused by diabetes leads to weakened immune response and initiates the transcription and translation of the inducible nitric oxide synthase (iNOS) gene to produce NO. Besides, the increased expression of carcinogens related to Nitric oxide synthase 2 (Nos2), such as Spp1, Mmp11, and Kitl, causes breast cancer to develop more rapidly. Here, NIR‐II imaging probe is applied first to study diabetes‐related breast cancer and certain reference value is provided for subsequent research on the mechanism of diabetes promoting the progression of breast cancer.