癌症研究
免疫疗法
光动力疗法
下调和上调
乳腺癌
免疫原性细胞死亡
免疫系统
光敏剂
癌症
转移性乳腺癌
车站3
医学
癌细胞
药理学
免疫学
化学
信号转导
生物
内科学
细胞生物学
生物化学
有机化学
基因
作者
Ziwen Qiu,Zhen-Ming Lü,Jiaqi Huang,Yingtao Zhong,Ning Yan,Ren‐Jiang Kong,Hong Cheng
出处
期刊:Biomaterials
[Elsevier]
日期:2023-12-01
卷期号:303: 122392-122392
被引量:1
标识
DOI:10.1016/j.biomaterials.2023.122392
摘要
Tumor cells overexpress programmed cell death ligand 1 (PD-L1) to impede immune responses and escape immune elimination. Development of effective combination regimens to sensitize immunotherapy is promising but always challenging. Herein, a self-reinforced photodynamic immunostimulator (designated as PCS) is constructed for metastatic breast cancer treatment through simultaneous downregulation and blockade of PD-L1. Specifically, PCS is prepared by encapsulating signal transducer and activator of transcription 3 (STAT3) inhibitor (Stattic) into photosensitizer (protoporphyrin IX) modified PD-L1 blockade peptide (CVRARTR) through drug self-assembly. PCS can facilitate the targeted drug accumulation in PD-L1 overexpressed breast cancer cells to block PD-L1 and inhibit the phosphorylation of STAT3 to downregulate PD-L1. Moreover, PCS increases intracellular oxidative stress to show a robust anti-proliferation effect through photodynamic therapy (PDT), which also triggers an immunogenic cell death (ICD) to expose the immunostimulatory signals. Consequently, the efficient PD-L1 inhibition and robust PDT of PCS synergistically suppress the malignant growth of breast cancer, and concurrently activate the systemic anti-tumor immunity for metastatic inhibition with no obvious side effects. Such a photodynamic immunostimulator may provide an effective combination regimen for therapies activated immunotherapy against metastatic breast cancer.
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