Yang Langyu, Wei Minyan, Deng Xiaohua, He Linlong, Lin Yinshan, Lin Xufeng, Zhou Dazhi, Li Ming, Qin Aiping, Zhang Lingmin, Ouyang Zizhang
The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People's Republic of China.
The Affiliated Panyu Central Hospital, The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, AIE Pharmaceutical Biology Innovation Research Center, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, People's Republic of China.
Int J Nanomedicine. 2025 Aug 24;20:10177-10194. doi: 10.2147/IJN.S536484. eCollection 2025.
BACKGROUND: Lung cancer has become one of the most fatal cancers at present. Traditional treatments showed limited therapeutic effects on lung cancer. The phototherapy has emerged as a powerful approach for lung cancer treatment. Aggregation-induced emission luminogens (AIEgens) exhibit excellent optical performance such as strong fluorescence, enhanced reactive oxygen species (ROS) generation, and effective thermal effect after aggregation, which show great potential in phototherapy. However, the disadvantages including hydrophobicity, low specificity, and short circulation lifetime limited their efficacy on cancer therapy. METHODS: We developed a biomimetic AIEgens constructed using CD8 T cells membrane to camouflage the AIEgen CHNOS (named BITT) nanoparticles (termed TB). The prepared TB improved the tumor accumulation of AIEgen by PD-1/PD-L1 recognition on the CD8 T and LLC cell membranes, respectively. RESULTS: The prepared TB showed improved binding efficiency, photothermal effects, and ROS generation ability to kill the lung cancer cells. TB also showed improved circulation lifetime and excellent tumor targeting ability, leading to effective phototherapy and immunotherapy in vivo based on BITT and the CD8 T cell-derived membranes. Based on the AIE and immune checkpoint blockade (ICB) strategies, TB enhanced the antitumor activities of lung cancer by phototherapy and immunotherapy. CONCLUSION: The present work developed a type of biomimetic AIEgens, which overcame the inherent limitations of conventional AIEgens and leveraged immune recognition for targeted tumor accumulation. Furthermore, the integration of AIE-driven phototherapy with immune checkpoint blockade demonstrated potent synergistic antitumor efficacy, establishing a promising combinatorial strategy against aggressive lung malignancies.
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