2. Academic Validation
  3. HIF-2α-targeted interventional chemoembolization multifunctional microspheres for effective elimination of hepatocellular carcinoma

HIF-2α-targeted interventional chemoembolization multifunctional microspheres for effective elimination of hepatocellular carcinoma

  • Biomaterials. 2022 May;284:121512. doi: 10.1016/j.biomaterials.2022.121512.
Minjiang Chen 1,  Gaofeng Shu 2,  Xiuling Lv 2,  Xiaoling Xu 3,  Chenying Lu 2,  Enqi Qiao 2,  Shiji Fang 2,  Lin Shen 2,  Nannan Zhang 2,  Jun Wang 3,  Chunmiao Chen 2,  Jingjing Song 2,  Zhuang Liu 4,  Yongzhong Du 5,  Jiansong Ji 6
Affiliations

Affiliations

  • 1 Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China.
  • 2 Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China.
  • 3 Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 4 Institute of Functional Nano & Soft Materials (FUNSOM), Key Lab Carbon Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China. Electronic address: zliu@suda.edu.cn.
  • 5 Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. Electronic address: duyongzhong@zju.edu.cn.
  • 6 Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China. Electronic address: jijiansong@zju.edu.cn.
PMID: 35405577 DOI: 10.1016/j.biomaterials.2022.121512
Abstract

Transcatheter arterial chemoembolization (TACE) is widely used for the treatment of advanced hepatocellular carcinoma (HCC). However, the long-term hypoxic microenvironment caused by TACE seriously affects the therapeutic effect of TACE. HIF-2α plays a crucial role on the chronic hypoxia process, which might be an ideal target for TACE therapy. Herein, a multifunctional polyvinyl alcohol (PVA)/hyaluronic acid (HA)-based microsphere (PT/DOX-MS) co-loaded with doxorubicin (DOX) and PT-2385, an effective HIF-2α inhibitor, was developed for enhanced TACE treatment efficacy. In vitro and in vivo studies revealed that PT/DOX-MS had a superior ability to treat HCC by blocking the tumor cells in G2/M phase, prompting cell Apoptosis, and inhibiting tumor angiogenesis. The antitumor mechanisms of PT/DOX-MS were possibly due to that the introduction of PT-2385 could effectively inhibit the expression level of HIF-2α in hypoxic HCC cells, thereby down-regulating the expression levels of Cyclin D1, VEGF and TGF-α. In addition, the combination of DOX and PT-2385 could jointly inhibit VEGF expression, which was another reason accounting for the combined anti-cancer effect of PT/DOX-MS. Overall, our study demonstrated that PT/DOX-MS is a promising embolic agent for enhanced HCC treatment via the combined effect of hypoxia microenvironment improvement, chemotherapy, and embolization.

Keywords

Drug-loading microsphere; HIF-2α; Hepatocellular carcinoma; Polyvinyl alcohol; Transcatheter arterial chemoembolization.

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