Photothermal Fe3O4 nanoparticles induced immunogenic ferroptosis for synergistic colorectal cancer therapy

被引:24
作者
Li, Yue [1 ,2 ,3 ]
Chen, Jia [1 ,2 ,6 ]
Xia, Qi [1 ,2 ]
Shang, Jing [1 ,2 ,5 ]
He, Yujie [1 ,2 ,6 ]
Li, Zhi [1 ,2 ]
Chen, Yingying [1 ,2 ,3 ]
Gao, Feng [4 ]
Yu, Xi [1 ,2 ,3 ]
Yuan, Zeting [1 ,2 ,3 ,4 ,5 ]
Yin, Peihao [1 ,2 ,5 ,6 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China
[2] Shanghai Univ Tradit Chinese, Putuo Hosp, Shanghai 200062, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Cent Lab, Shanghai 200062, Peoples R China
[4] East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China
[5] Anhui Med Univ, Shanghai Putuo Cent Sch Clin Med, Shanghai 200062, Peoples R China
[6] Chengdu Univ Tradit Chinese Med, Sch Med & Life Sci, Chengdu 610075, Peoples R China
基金
中国博士后科学基金;
关键词
Photothermal therapy; Ferroptosis; ICD; Immunotherapy; CRC; IMMUNOTHERAPY;
D O I
10.1186/s12951-024-02909-3
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Photothermal therapy (PTT) is a promising non-invasive treatment that has shown great potential in eliminating tumors. It not only induces apoptosis of cancer cells but also triggers immunogenic cell death (ICD) which could activate the immune system against cancer. However, the immunosuppressive tumor microenvironment (TIME) poses a challenge to triggering strong immune responses with a single treatment, thus limiting the therapeutic effect of cancer immunotherapy. In this study, dual-targeted nano delivery system (GOx@FeNPs) combined with alpha PD-L1 immune checkpoint blocker could inhibit colorectal cancer (CRC) progression by mediating PTT, ferroptosis and anti-tumor immune response. Briefly, specific tumor delivery was achieved by the cyclic arginine glycyl aspartate (cRGD) peptide and anisamide (AA) in GOx@FeNPs which not only had a good photothermal effect to realize PTT and induce ICD, but also could deplete glutathione (GSH) and catalyze the production of reactive oxygen species (ROS) from endogenous H2O2. All these accelerated the Fenton reaction and augmented the process of PTT-induced ICD. Thus, a large amount of tumor specific antigen was released to stimulate the maturation of dendritic cells (DCs) in lymph nodes and enhance the infiltration of CD8(+) T cells in tumor. At the same time, the combination with alpha PD-L1 has favorable synergistic effectiveness against CRC with tumor inhibition rate over 90%. Furthermore, GOx@FeNPs had good magnetic resonance imaging (MRI) capability under T2-weighting owing to the presence of Fe3+, which is favorable for integrated diagnosis and treatment systems of CRC. By constructing a dual-targeted GOx@FeNPs nanoplatform, PTT synergistically combined with ferroptosis was realized to improve the immunotherapeutic effect, providing a new approach for CRC immunotherapy.
引用
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页数:17
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