Langyu Yang,1,2,* Minyan Wei,1,2,* Xiaohua Deng,1,2,* Linlong He,1,2 Yinshan Lin,1,2 Xufeng Lin,1,2 Dazhi Zhou,1,2 Ming Li,3 Aiping Qin,1,2 Lingmin Zhang,1,2 Zizhang Ouyang1 

1The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People’s Republic of China; 2The 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; 3Medical Research Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lingmin Zhang, Email zhanglm@gzhmu.edu.cn Zizhang Ouyang, Email 2019695272@gzhmu.edu.cn

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 C41H37N2O3S2 (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.

Keywords: aggregation-induced emission luminogens, T cells, phototherapy, immune checkpoint blockade, lung cancer