Integration of Multi‐Rotor and Multi‐Conjugation: Ultrahigh Absorption Coefficient Dye Enables NIR‐II Fluorescence Imaging‐guided Photothermal Immunotherapy

Abstract The progressive accumulation of mutated genes in cancer cells facilitates tumor immune escape. Photothermal immunotherapy addresses this problem by triggering immunogenic cell death (ICD) through photothermal treatment, releasing endogenous immunogenic neoantigens. Herein, guided by the “multi‐rotor & multi‐conjugation” concept, near‐infrared region II (NIR‐II) cyanine molecules are designed with varying numbers of benzene rotors. TPE‐CyA, with more benzene rotors, features an ultra‐high molar extinction coefficient (1.786 × 10 5 m −1 cm −1 ), a well‐balanced fluorescence quantum yield (0.99%), and a 45.72% photothermal conversion efficiency. TPE‐CyA nanoparticles (TPE‐CyA NPs) are ideal for high‐resolution NIR‐II fluorescence imaging and angiography. Imaging‐guided TPE‐CyA NPs show great potential in NIR‐II photothermal immunotherapy by effectively suppressing bilateral tumor growth and liver metastasis without additional immunoadjuvants. Moreover, the photothermal immunotherapy guided by TPE‐CyA NPs can induce ICD, promote dendritic cell (DCs) maturation, increase T‐cell infiltration in tumors, and activate systemic immunity to prevent metastasis and recurrence. This research highlights the potential of NIR‐II photothermal therapy in tumor cell ablation, immune activation for cancer and vascular diagnostics, presenting a novel strategy for both primary and metastatic cancers.