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A Versatile 980 nm Absorbing Aggregation-Induced Emission Luminogen for NIR-II Imaging-Guided Synergistic Photo-Immunotherapy Against Advanced Pancreatic Cancer
Advanced Functional Materials ( IF 19.0 ) Pub Date : 2022-06-24 , DOI: 10.1002/adfm.202205371
Miao Wang 1 , Dingyuan Yan 2 , Meng Wang 3 , Qian Wu 4 , Ruixiang Song 1 , Yiming Huang 1 , Jie Rao 1 , Dong Wang 2 , Feifan Zhou 1 , Ben Zhong Tang 2, 4, 5
Affiliation  

To address urgent tasks in the treatment of advanced deep-seated tumors, a 980 nm absorbing agent with aggregation-induced emission tendency, namely TPE-BT-BBTD, which simultaneously possesses the longest absorption wavelength among all the reported AIE molecules is developed. The functionality of deep near-infrared-II fluorescence imaging (NIR-II FLI) and outstanding photothermal performance is well-tailored for advanced pancreatic cancer treatment. With the covalent attachment of the programmed death-ligand 1 (αPD-L1) antibody, αPD-L1@TPE-BT-BBTD nanoparticles show precise tumor targeting and excellent immunosuppression reversal ability. Following local photothermal therapy, immunogenic tumor vaccination is induced to trigger the infiltration of cytotoxic T lymphocytes (CTLs) in tumors. With the decreased FoxP3+ Treg cells and M2-like macrophages that are reversed by αPD-L1, CTLs activity is further enhanced with more production of granzyme B (GrB), which much accurately leads to tumor apoptosis and effectively suppressed spontaneous metastases. Overall, αPD-L1@TPE-BT-BBTD nanoparticles based NIR-II FLI-mediated photo-immunotherapy is able to significantly improve the control of primary tumor and metastasis in the treatment of advanced deep-seated tumors.

中文翻译:

用于 NIR-II 成像引导的协同光免疫治疗晚期胰腺癌的多功能 980 nm 吸收聚集诱导发射发光剂

为了解决晚期深部肿瘤治疗中的紧迫任务,开发了一种具有聚集诱导发射倾向的980 nm吸收剂,即TPE-BT-BBTD,它同时具有所有报道的AIE分子中最长的吸收波长。深近红外 II 荧光成像 (NIR-II FLI) 的功能和出色的光热性能非常适合晚期胰腺癌治疗。通过程序性死亡配体 1 (αPD-L1) 抗体的共价连接,αPD-L1@TPE-BT-BBTD 纳米颗粒显示出精确的肿瘤靶向性和出色的免疫抑制逆转能力。在局部光热疗法之后,诱导免疫原性肿瘤疫苗接种以触发肿瘤中细胞毒性 T 淋巴细胞 (CTL) 的浸润。随着 FoxP3 +的降低被αPD-L1逆转的Treg细胞和M2样巨噬细胞,CTLs活性随着颗粒酶B(GrB)的产生而进一步增强,这更准确地导致肿瘤细胞凋亡并有效抑制自发转移。总体而言,基于αPD-L1@TPE-BT-BBTD纳米粒子的NIR-II FLI介导的光免疫疗法能够显着改善晚期深部肿瘤治疗中对原发性肿瘤和转移的控制。
更新日期:2022-06-24
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