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.

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 H 2 O 2 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.