Reshaping Immunosuppressive Tumor Microenvironment Using Ferroptosis/Cuproptosis Nanosensitizers for Enhanced Radioimmunotherapy

被引：2

作者：

He, Chenxi ^{[1
,2
]}

Zhu, Nan ^{[2
,3
]}

Chen, Ying ^{[2
,3
]}

Zheng, Yinfei ^{[1
,2
]}

Chen, Siwen ^{[2
]}

Wu, Zede ^{[1
,2
]}

Zheng, Shuting ^{[1
,2
]}

Hu, Honglei ^{[4
]}

Qi, Li ^{[5
]}

Hou, Meirong ^{[1
]}

Shen, Zheyu ^{[5
]}

Zhao, Bingxia ^{[2
,6
]}

Guo, Weihong ^{[3
]}

Yan, Chenggong ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Med Imaging Ctr, Guangzhou 510515, Peoples R China

[2] Southern Med Univ, Canc Res Inst, Guangzhou Key Lab Tumor Immunol Res, Sch Basic Med Sci, Guangzhou 510515, Peoples R China

[3] Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Peoples R China

[4] Guangzhou Med Univ, Dept Radiol, Affiliated Hosp 2, Guangzhou 510260, Peoples R China

[5] Southern Med Univ, Sch Biomed Engn, Guangzhou 510515, Guangdong, Peoples R China

[6] Southern Med Univ, Expt Educ Adm Ctr, Sch Basic Med Sci, Guangzhou 510515, Peoples R China

来源：

ADVANCED FUNCTIONAL MATERIALS | 2024年

基金：

中国国家自然科学基金;

关键词：

cuproptosis; immunotherapy; molecular imaging; radiotherapy; tumor microenvironment; COLORECTAL-CANCER; RADIOTHERAPY; BLOCKADE;

D O I：

10.1002/adfm.202409966

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Radiotherapy, a traditional cancer treatment, not only controls local tumor growth but also potentially induces immunogenic cell death, initiating systemic immune responses. However, radiotherapy resistance and immunosuppressive tumor microenvironments often limit the potency of radiation-induced anti-tumor immune responses, rendering them insufficient for clinical applications. Consequently, trimetallic nanoparticles are constructed with dual enzymatic activity, AuBiCu-distearoyl phosphoethanolamine-PEG nanoparticles (AuBiCu-PEG NPs), to synergistically improve radiotherapy resistance through X-ray deposition, hypoxia alleviation, and ferroptosis and cuproptosis induction. This approach promotes radiotherapy-induced immunogenic cell death and boosts anti-tumor immune responses. Furthermore, AuBiCu-PEG NPs effectively reversed radiation-induced upregulation of programmed cell death 1 ligand 1 (PD-L1), inhibit tumor immune evasion, and reshaped the immune microenvironment. Non-invasive and real-time longitudinal monitoring of nanoparticle accumulation in tumors can be achieved using spectral computed tomography (CT) and photoacoustic (PA) imaging. In summary, the designed AuBiCu-PEG NPs serve as promising nanoplatforms for immune microenvironment remodeling and can be used in multimodal molecular imaging-guided ferroptosis-cuproptosis-enhanced radiotherapy. To overcome the radiotherapy resistance and regulate the immunesuppressive tumor microenvironment, a strategy of trimetallic AuBiCu-PEG nanoparticles is proposed in this study. Due to their high-Z properties, the nano-sensitizer can enhance the efficacy of radiotherapy, induce immunogenic cell death and ferroptosis/cuproptosis to evoke tumor immunogenicity. Additionally, the spectral CT and photoacoustic imaging facilitate noninvasive monitoring of nanoparticle accumulation in tumors. image

引用

页数：15