期刊
NANOSCALE ADVANCES
卷 4, 期 22, 页码 4847-4862出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d2na00322h
关键词
-
资金
- Medical College of Three Gorges University
- Hubei Key Laboratory of the Tumor Microenvironment and Immunotherapy Foundation [2018KZL02, 2019KZL10]
- National Natural Science Foundation of China [81673675]
Nanobubbles carrying immune check inhibitors and sonodynamic agents were prepared to inhibit hepatocellular carcinoma (HCC) growth by regulating immune cell function and inducing immunogenic tumor cell death. These nanobubbles showed promising potential in enhancing anti-cancer immune responses.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, posing a global threat to human healthcare, and current approved treatment strategies do not produce satisfactory outcomes. Here, nanobubbles (NBs) were prepared that carried Immune Check Inhibitors (ICIs), PD-L1 antibody (PD-L1 Ab) and sonodynamic agent CHLORIN E6 (Ce-6); the anti-cancer properties of these NBs were analyzed from the point of view of immune and sonodynamic therapies. The PD-L1 Ab/Ce-6-NBs could inhibit tumor growth through regulating reactive oxygen species (ROS) production, apoptosis, and most importantly, the function of associated immunocytes, including natural killer cells and lymphocytes. The tumor tissues highly expressed markers of immunogenic tumor cell death (ICD) in which the expression of calreticulin (CRT) and ICD-related immune cytokines (CD80, CD86, INF-gamma, and IL-2) were increased in PD-L1 Ab/Ce-6-NB treated mice. PD-L1 Ab/Ce-6-NBs also promoted murine spleen lymphocyte proliferation and cytotoxic activity, as well as CD8+ T cell infiltration in the tumor tissues, and downregulation of the PD-L1 protein and mRNA expression. Furthermore, Bax expression was increased and Bcl-2 was inhibited at the mRNA and protein levels in a murine subcutaneous transplanted tumor model. These results indicate that PD-L1 Ab/Ce-6-NBs can induce ROS-dependent ICD to further boost anti-cancer immune responses under the action of targeting the PD-1/PD-L1 immune check point in the tumor microenvironment as a promising therapeutic agent for HCC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据