Photodynamicand Photothermal Co-Induced EfficientAnti-Tumor Immunotherapy

Currently, immunotherapy based on photothermal and the application of photodynamic therapy in anti-tumor treatment is showing great potential. Its uniqueness lies in the critical role of small molecule immunomodulators in promoting effective immune responses against tumors, and the use of laser-activated biophysical mechanisms to precisely trigger the swift demise of cancer cells, avoiding damage to surrounding normal tissues. However, the use of photodynamic therapy (PDT) alone is hampered by the tumors’ hypoxic environment, resulting in poor antitumor effects, while photothermal therapy (PTT) alone cannot arouse enough antigen presentation. It is of great significance to design photosensitizers (PSs) that possess both PDT and PTT effects. Herein, a series of PSs with both PDT and PTT efficacy are reported, ultimately selecting Cy7-Naph as the star molecule due to its best overall phototherapeutic effect. Upon reactive oxygen species (ROS) production and thermogenesis in tumor cells, Cy7-Naph induced significant apoptosis and eventually boosted the release of damage-associated molecular patterns (DAMPs) under near-infrared (NIR) light irradiation. By combining Cy7-Naph with the Toll-like receptor agonist Resiquimod (R848), a synergistic treatment for bilateral tumor-bearing mice is achieved. This combination promotes dendritic cell (DC) maturation and increases the infiltration of cytotoxic T lymphocytes (CTLs), leading to significant inhibition of both primary and distant tumors.