Pyroptosis‐Mediated Synergistic Photodynamic and Photothermal Immunotherapy Enabled by a Tumor‐Membrane‐Targeted Photosensitive Dimer

• Published in: Advanced materials (Weinheim) Vol. 35; no. 25; pp. e2300232 - n/a
• Main Authors: Tang, Yuqi, Bisoyi, Hari Krishna, Chen, Xu‐Man, Liu, Zhiyang, Chen, Xiao, Zhang, Shu, Li, Quan
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.06.2023
• Subjects: aggregation‐induced emission; Anticancer properties; Antigens; Apoptosis; Cancer; Cell death; Cell membranes; Damage patterns; Dimers; Immunosuppression; Immunotherapy; Materials science; photosensitive dimer; Photosensitivity; pyroptosis; Synergistic effect; synergistic photodynamic and photothermal immunotherapy; tumor cell membrane targeting; Tumors; aggregation-induced emission; pyroptosis; tumor cell membrane targeting; synergistic photodynamic and photothermal immunotherapy; photosensitive dimer
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.202300232

Overcoming the resistance to apoptosis and immunosuppression of tumor cells is a significant challenge in augmenting the effect of cancer immunotherapy. Pyroptosis, a lytic programmed cell‐death pathway unlike apoptosis, is considered a type of immunogenic cell death (ICD) that can intensify the ICD process in tumor cells, releasing dramatically increased tumor‐associated antigens and damage‐associated molecular patterns to promote cancer immunotherapy. Herein, a tumor cell membrane‐targeted aggregation‐induced emission photosensitive dimer is found to be able to achieve highly efficient ICD under the synergistic effect of photodynamic and photothermal therapy. The photosensitive dimer can efficiently produce type‐I reactive oxygen species (ROS) by photodynamic therapy in hypoxic tumor tissue, leading to pyroptosis by direct cell membrane damage, which is further reinforced by its photothermal effect. Furthermore, the enhanced ICD effect based on the dimer can completely eliminate the primary tumor on the seventh day of treatment and can also boost systemic antitumor immunity by generating immune memory, which is demonstrated by the superior antitumor therapeutic effects on both solid tumors and metastatic tumors when healing 4T1 tumor mouse models with poor immunogenicity. A membrane‐targeted photosensitive dimer, which effectively generates type‐I reactive oxygen species in hypoxic tumor tissue for pyroptosis‐mediated photoimmunotherapy, is successfully developed. Its remarkable photothermal properties accelerate the pyroptosis process, increase DNA damage in tumor cells, generate drastic immunogenic cell death and systemic antitumor immune response, and prevent tumor recurrence and metastasis.