A Silver‐Induced Absorption Red‐Shifted Dual‐Targeted Nanodiagnosis‐Treatment Agent for NIR‐II Photoacoustic Imaging‐Guided Photothermal and ROS Simultaneously Enhanced Immune Checkpoint Blockade Antitumor Therapy

Abstract Tumor metastasis remains a leading factor in the failure of cancer treatments and patient mortality. To address this, a silver‐induced absorption red‐shifted core‐shell nano‐particle is developed, and surface‐modified with triphenylphosphonium bromide (TPP) and hyaluronic acid (HA) to obtain a novel nanodiagnosis‐treatment agent (Ag@CuS‐TPP@HA). This diagnosis‐treatment agent can dual‐targets cancer cells and mitochondria, and exhibits maximal light absorption at 1064 nm, thereby enhancing nesr‐infrared II (NIR‐II) photoacoustic (PA) signal and photothermal effects under 1064 nm laser irradiation. Additionally, the silver in Ag@CuS‐TPP@HA can catalyze the Fenton‐like reactions with H₂O₂ in the tumor tissue, yielding reactive oxygen species (ROS). The ROS production, coupled with enhanced photothermal effects, instigates immunogenic cell death (ICD), leading to a substantial release of tumor‐associated antigens (TAAs) and damage‐associated molecular patterns, which have improved the tumor immune suppression microenvironment and boosting immune checkpoint blockade therapy, thus stimulating a systemic antitumor immune response. Hence, Ag@CuS‐TPP@HA, as a cancer diagnostic‐treatment agent, not only accomplishes targeted the NIR‐II PA imaging of tumor tissue and addresses the challenge of accurate diagnosis of deep cancer tissue in vivo, but it also leverages ROS/photothermal therapy to enhance immune checkpoint blockade, thereby eliminating primary tumors and effectively inhibiting distant tumor growth.