Dynamic Adjust of Non‐Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR‐II Imaging Mediated Photothermal Therapy and Immunotherapy

• Published in: Advanced science Vol. 9; no. 8; pp. e2104793 - n/a
• Main Authors: Wang, Zhenjie, Yu, Ling, Wang, Yuehua, Wang, Chenlu, Mu, Qingchun, Liu, Xiaojing, Yu, Meng, Wang, Kang‐Nan, Yao, Guangyu, Yu, Zhiqiang
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.03.2022; John Wiley and Sons Inc
• Subjects: Adenosine; AIE; Cancer therapies; CD39‐CD73‐A2AR; Chemotherapy; Efficiency; immunogenic cell death; Immunotherapy; Lasers; Nanoparticles; Nanoparticles - therapeutic use; NIR‐II; Phototherapy - methods; Photothermal Therapy; Prodrugs - pharmacology; NIR-II; AIE; CD39-CD73-A2AR; immunogenic cell death; photothermal therapy
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202104793

Due to the aggregation‐caused quenching effect and near‐infrared I poor penetration capabilities of common fluorescent molecules, their applications in visualized imaging and photoactivated treatment are limited. Therefore, new near‐infrared II (NIR‐II) molecule (named TST), which had the abilities of aggregation‐induced emission (AIE) and photothermal therapy are synthesized. Moreover, in order to further improve its fluorescent yield and therapeutic effect, camptothecin prodrug (CPT‐S‐PEG) and novel immune checkpoint inhibitor AZD4635 are used to co‐assemble with TST into nanoparticles for drug delivery. On account of the strong interaction of camptothecin and TST, the intramolecular rotation of TST is limited, thereby inhibiting non‐radiation attenuation and promoting fluorescence generation when the nanoparticles are intact. As nanoparticles uptake by cancer cells, redox sensitive CPT‐S‐PEG is degraded and the nanoparticles disintegrate. The released TST enhances non‐radiative attenuation and expedites photothermal conversion because of the removal of the constraint of camptothecin. Furthermore, photothermal therapy induces immunogenic cell death of cancer cells and releases abundant ATP into the tumor microenvironment to recruit immune cells. However, superfluous ATP is converted into immunosuppressive adenosine through the CD39‐CD73‐A2AR pathway. The AZD4635 released by photothermal disintegration of the nanoparticles just blocks this pathway timely, achieving favorable synergistic effect of photothermal therapy, chemotherapy, and immunotherapy. By dynamically adjusting the radiative attenuation and non‐radiative attenuation of aggregation‐induced emission molecules, the effect of enhancing near infrared region II imaging and photothermal therapy can be achieved simultaneously. Moreover, photothermal therapy cause immunogenic cell death. The released camptothecin inhibits DNA topoisomerase to play a role in chemotherapy and the released AZD4635 restrains CD39‐CD73‐A2AR pathway to enhance immunotherapy.