Citation: Jianpeng Sheng, Jiangchao Wu, Xianghong Yin, Zhu Sun, Xun Wang, Junlei Zhang, Jianghui Tang, Yongtao Ji, Jinyuan Song, Xiaobao Wei, Lin Wang, Yaxing Zhao, Hui Zhang, Taohong Li, Qi Zhang, Xueli Bai, Li Chen, Dong Chen, Tingbo Liang. Synergetic treatment of oxygen microcapsules and lenvatinib for enhanced therapy of HCC by alleviating hypoxia condition and activating anti-tumor immunity[J]. Chinese Chemical Letters, ;2023, 34(4): 107738. doi: 10.1016/j.cclet.2022.08.018 shu

Synergetic treatment of oxygen microcapsules and lenvatinib for enhanced therapy of HCC by alleviating hypoxia condition and activating anti-tumor immunity

Jianpeng Sheng ^{a, b, c, 1} ,
Jiangchao Wu ^{a, b, c, 1} ,
Xianghong Yin ^{d, 1} ,
Zhu Sun ^e ,
Xun Wang ^{a, b, c} ,
Junlei Zhang ^{a, b, c} ,
Jianghui Tang ^{a, b, c} ,
Yongtao Ji ^{a, b, c} ,
Jinyuan Song ^{a, b, c} ,
Xiaobao Wei ^{a, b, c} ,
Lin Wang ^{a, b, c} ,
Yaxing Zhao ^{a, b, c} ,
Hui Zhang ^{a, b, c} ,
Taohong Li ^{a, b, c} ,
Qi Zhang ^{a, b, c} ,
Xueli Bai ^{a, b, c} ,
Li Chen ^e ,
Dong Chen ^{e, f, *,} ,
Tingbo Liang ^{a, b, c, *,}

a.
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310002, China
b.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310002, China
c.
Zhejiang University Cancer Center, Zhejiang University, Hangzhou 310002, China
d.
School of Basic Medical Sciences, Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou 325035, China
e.
College of Energy Engineering and State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou 310027, China
f.
Department of Medical Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

chen_dong@zju.edu.cn

liangtingbo@zju.edu.cn

Received Date: 28 March 2022
Revised Date: 4 August 2022
Accepted Date: 8 August 2022
Available Online: 10 August 2022

Figures(8)

Hypoxia is a typical characteristic of hepatocellular carcinoma (HCC), which causes tremendous obstacles to tumor treatments. Current first-line treatment may further deteriorate tumor hypoxia. For example, Lenvatinib, a receptor tyrosine kinase inhibitor (RTKI), suppresses tumor growth via blocking vascular endothelial growth factor (VEGF) signaling, and can also inhibit angiogenesis, thus limiting oxygen supply to tumor sites. Therefore, alleviating tumor microenvironment (TME) hypoxia holds great potential for enhancing the therapeutic effect of RTKI. Here, nanoparticle-stabilized oxygen microcapsules, a stable and biocompatible oxygen-loaded delivery system, are successfully prepared through interfacial polymerization of polydopamine nanoparticles. The microcapsules with a large loading capacity of oxygen in the core show excellent bioavailability and dispersity, which could effectively improve the hypoxic TME when they serve as oxygen delivery vehicles. Synergetic treatments of Lenvatinib and oxygen microcapsules could induce the transition of “cold tumor” in an immune-suppressed state to “hot tumor” in an immune-activated state by improving tumor hypoxic TME and reducing angiogenesis in HCC. It is revealed that combined treatments of oxygen microcapsules and Lenvatinib could polarize tumor-associated macrophages (TAMs) to anti-tumor M1 cells and activate T cell-mediated anti-tumor immune responses. The results suggest that synergetic therapy using oxygen microcapsules and Lenvatinib could alleviate the hypoxic TME and enhance the therapeutic performance of RTKI, demonstrating a promising anti-tumor strategy for enhanced therapy of HCC.
- Hypoxia,
- Oxygen microcapsules,
- Lenvatinib,
- Immune,
- Hepatocellular carcinoma
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沈阳化工大学材料科学与工程学院沈阳 110142