In-situ-formed immunotherapeutic and hemostatic dual drug-loaded nanohydrogel for preventing postoperative recurrence of hepatocellular carcinoma

Ke, Jianji; Liu, Yahui; Liu, Feiqi; Cai, Hongqiao; Li, Xiaocheng; Zhang, Zhiyuan; Wang, Ning; Shao, Bingru; Wang, Zhihua; Han, Mingda; Ji, Bai

doi:10.1016/j.jconrel.2024.06.030

Journal of Controlled Release

2024

DOI: 10.1016/j.jconrel.2024.06.030

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In-situ-formed immunotherapeutic and hemostatic dual drug-loaded nanohydrogel for preventing postoperative recurrence of hepatocellular carcinoma

Jianji Ke,

Yahui Liu,

Feiqi Liu

et al.

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2024

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Enhancing Radiofrequency Ablation for Hepatocellular Carcinoma: Nano‐Epidrug Effects on Immune Modulation and Antigenicity Restoration

Li,

Liu,

et al. 2024

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Radiofrequency ablation (RFA), a critical therapy for hepatocellular carcinoma (HCC), carries a significant risk of recurrence and metastasis, particularly owing to mechanisms involving immune evasion and antigen downregulation via epigenetic modifications. This study introduces a “nano‐epidrug” named MFMP. MFMP, which is composed of hollow mesoporous manganese dioxide (MnO2) nanoparticles, FIDAS‐5 as an MAT2A inhibitor, macrophage membrane, and anti‐PD‐L1 (aPD‐L1), targets HCC cells. By selectively binding to these cells, MFMP initially reverses immune suppression via PD‐L1 inhibition. After endocytosis, MFMP disassembles in the tumor microenvironment, releasing FIDAS‐5 and Mn2+. FIDAS‐5 prevents cGAS methylation, whereas Mn2+ aids STING pathway restoration. In addition, FIDAS‐5 reduces m6A RNA modification, suppressing EGFR expression. These changes enhance HCC antigenicity to promote cytotoxic T cell recognition and cytotoxic killing. Furthermore, MFMP mediates immunogenic cell death in HCC by synergizing with RFA through cGAS DNA demethylation, EGFR mRNA demethylation, and TBK1 protein phosphorylation, thereby inhibiting recurrence and metastasis and enhancing immune memory. Thus, MFMP is a potential adjunctive therapy requiring clinical validation.

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Enhancing Radiofrequency Ablation for Hepatocellular Carcinoma: Nano‐Epidrug Effects on Immune Modulation and Antigenicity Restoration

Li,

Liu,

et al. 2024

Advanced Materials

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show abstract

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In-situ-formed immunotherapeutic and hemostatic dual drug-loaded nanohydrogel for preventing postoperative recurrence of hepatocellular carcinoma

Cited by 1 publication

References 63 publications

Enhancing Radiofrequency Ablation for Hepatocellular Carcinoma: Nano‐Epidrug Effects on Immune Modulation and Antigenicity Restoration

Enhancing Radiofrequency Ablation for Hepatocellular Carcinoma: Nano‐Epidrug Effects on Immune Modulation and Antigenicity Restoration

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