Sonodynamic Therapy-Driven Immunotherapy: Constructing AIE Organic Sonosensitizers Using an Advanced Receptor-Regulated Strategy

被引：9

作者：

Tian, Mengyan ^{[1
]}

Li, Yucong ^{[2
]}

Li, Yaning ^{[1
]}

Yang, Tianyue ^{[1
]}

Chen, Hongli ^{[3
]}

Guo, Jun ^{[2
]}

Liu, Yi ^{[4
,5
,6
]}

Liu, Pai ^{[1
]}

机构：

[1] Tiangong Univ, Sch Mat Sci & Engn, State Key Lab Separat Membranes & Membrane Proc, Tianjin 300387, Peoples R China

[2] Tiangong Univ, Sch Chem Engn & Technol, State Key Lab Separat Membranes & Membrane Proc, Tianjin 300387, Peoples R China

[3] Tiangong Univ, Sch Life Sci, State Key Lab Separat Membranes & Membrane Proc, Tianjin 300387, Peoples R China

[4] Tiangong Univ, Sch Chem, State Key Lab Separat Membrane & Membrane Proc, Tianjin 300387, Peoples R China

[5] Tiangong Univ, Sch Chem, Tianjin Key Lab Green Chem Technol & Proc Engn, Tianjin 300387, Peoples R China

[6] Wuhan Polytech Univ, Sch Chem & Environm Engn, Wuhan 430023, Peoples R China

来源：

SMALL | 2024年 / 20卷 / 37期

基金：

中国国家自然科学基金;

关键词：

aggregation-induced emission; mitochondrial oxidative stress; pH-switchable; receptor regulation strategy; sonodynamic therapy-driven immunotherapy; TUMOR MICROENVIRONMENT; NANOPARTICLES; EMISSION;

D O I：

10.1002/smll.202400654

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Benefit from the deeper penetration of mechanical wave, ultrasound (US)-based sonodynamic therapy (SDT) executes gratifying efficacy in treating deep-seated tumors. Nevertheless, the complicated mechanism of SDT undeniably hinders the exploration of ingenious sonosensitizers. Herein, a receptor engineering strategy of aggregation-induced emission (AIE) sonosensitizers (TPA-Tpy) with acceptor (A)-donor (D)-A' structure is proposed, which inspects the effect of increased cationizations on US sensitivity. Under US stimulation, enhanced cationization in TPA-Tpy improves intramolecular charge transfer (ICT) and accelerates charge separation, which possesses a non-negligible promotion in type I reactive oxygen species (ROS) production. Moreover, abundant ROS-mediated mitochondrial oxidative stress triggers satisfactory immunogenic cell death (ICD), which further promotes the combination of SDT and ICD. Subsequently, subacid pH-activated nanoparticles (TPA-Tpy NPs) are constructed with charge-converting layer (2,3-dimethylmaleic anhydride-poly (allylamine hydrochloride)-polyethylene glycol (DMMA-PAH-PEG)) and TPA-Tpy, achieving the controllable release of sonosensitizers. In vivo, TPA-Tpy-mediated SDT effectively initiates the surface-exposed of calreticulin (ecto-CRT), dendritic cells (DCs) maturation, and CD8+ T cell infiltration rate through enhanced ROS production, achieving suppression and ablation of primary and metastatic tumors. This study provides new opinions in regulating acceptors with eminent US sensitization, and brings a novel ICD sono-inducer based on SDT to realize superior antitumor effect. The innovative receptor engineering strategy inspects the effect of increased cationizations on US sensitivity. Abundant ROS-mediated mitochondrial oxidative stress triggers satisfactory ICD, which further promotes the combination of SDT and ICD. Moreover, a nanosystem of AIE sonosensitizer with pH-responsive is constructed, which obtain remarkably enhanced SDT-mediated anti-tumor therapy and ICD-inducing ability in vitro and vivo, and incite systemic immune response. image

引用

页数：13