Valence-Change MnO 2 -Coated Arsenene Nanosheets as a Pin1 Inhibitor for Hepatocellular Carcinoma Treatment.
Jingguo WangSiping LiangDongdong ZhuXiaocao MaQin PengGuanzhao WangYuting WangTiantian ChenMinhao WuTony Ye HuYuanqing ZhangPublished in: Journal of the American Chemical Society (2024)
The heterogeneity of hepatocellular carcinoma (HCC) can prevent effective treatment, emphasizing the need for more effective therapies. Herein, we employed arsenene nanosheets coated with manganese dioxide and polyethylene glycol (AMPNs) for the degradation of Pin1, which is universally overexpressed in HCC. By employing an "AND gate", AMPNs exhibited responsiveness toward excessive glutathione and hydrogen peroxide within the tumor microenvironment, thereby selectively releasing As x O y to mitigate potential side effects of As 2 O 3 . Notably, AMPNs induced the suppressing Pin1 expression while simultaneously upregulation PD-L1, thereby eliciting a robust antitumor immune response and enhancing the efficacy of anti-PD-1/anti-PD-L1 therapy. The combination of AMPNs and anti-PD-1 synergistically enhanced tumor suppression and effectively induced long-lasting immune memory. This approach did not reveal As 2 O 3 -associated toxicity, indicating that arsenene-based nanotherapeutic could be employed to amplify the response rate of anti-PD-1/anti-PD-L1 therapy to improve the clinical outcomes of HCC patients and potentially other solid tumors (e.g., breast cancer) that are refractory to anti-PD-1/anti-PD-L1 therapy.
Keyphrases
- hydrogen peroxide
- immune response
- end stage renal disease
- poor prognosis
- high glucose
- diabetic rats
- nitric oxide
- chronic kidney disease
- newly diagnosed
- signaling pathway
- oxidative stress
- ejection fraction
- single cell
- working memory
- body mass index
- reduced graphene oxide
- drug induced
- dendritic cells
- peritoneal dialysis
- physical activity
- combination therapy
- binding protein
- metal organic framework
- highly efficient
- gold nanoparticles
- human health
- young adults
- visible light