Nanomedicine-mediated induction of immunogenic cell death and prevention of PD-L1 overexpression for enhanced hepatocell
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Cancer Nanotechnology Open Access
RESEARCH
Nanomedicine‑mediated induction of immunogenic cell death and prevention of PD‑L1 overexpression for enhanced hepatocellular carcinoma therapy Hanzhang Zhu, Weijiang Zhou, Yafeng Wan, Ke Ge, Jun Lu and Changku Jia* *Correspondence: [email protected] Department of Hepatopancreatobiliary Surgery, Hangzhou First People’s Hospital, The Affiliated Hospital of Medical School of Zhejiang University, Hangzhou 310006, Zhejiang, China
Abstract Background: The present study aims to develop a nanoparticle encapsulating doxorubicin (DOX) and programmed death-ligand 1 (PD-L1) siRNA and evaluate its antitumor effects on hepatoma carcinoma (HCC). Methods: Nanoparticle encapsulating DOX and PD-L1 siRNA (NPDOX/siPD-L1) was characterized by dynamic light scattering and transmission electron microscopy. Flow cytometry was applied to analyze cell populations, NPDOX/siPD-L1 internalization, and cell apoptosis. Real-Time (RT)-quantitative reverse transcription (qPCR) and western blotting were used to determine the mRNA and protein levels, respectively. Released ATP was determined using ATP determination kit and cytokines were determined using specific ELISAs. A tumor-bearing animal model was established to evaluate the antitumor effects of NPDOX/siPD-L1. Results: Treatment of N PDOX/siPD-L1 induced immunogenic cell death (ICD) and PD-L1 overexpression in HCC. In vivo study demonstrated that intravenously injection of NPDOX/siPD-L1 significantly inhibited the tumor volume and PD-L1 expressions of tumor tissue in the H22 tumor-bearing animal model. Besides, the treatment of N PDOX/siPD-L1 also regulated the populations of matured dendritic cells and cytotoxic T cells and the productions of cytokines in the tumor tissues. Conclusion: Taken together, NPDOX/siPD-L1 showed significant anti-tumor effects on HCC by the induction of ICD and inhibition of PD-L1 overexpression. Keywords: Hepatocellular carcinoma, Nanoparticle, Doxorubicin, Immunogenic cell death, PD-L1
Background Hepatoma, also called hepatocellular carcinoma (HCC), is one of the most frequent malignant cancers worldwide (Bosch et al. 2004). The morbidity and mortality of HCC are globally ranked as third and fifth, respectively. It is known that about 8% of people suffering from hepatitis, who are ease to develop into HCC (Bosch et al. 2004; Sia et al. 2017). Besides, nonalcoholic fatty liver diseases and cirrhosis are also reported to © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Cr
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