Targeting SUMOylation with an injectable nanocomposite hydrogel to optimize radiofrequency ablation therapy for hepatocellular carcinoma.

Autor: Liu J; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Center of Cerebrovascular Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China., Li X; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. lixi57@mail.sysu.edu.cn.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. lixi57@mail.sysu.edu.cn.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. lixi57@mail.sysu.edu.cn., Chen J; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Center of Cerebrovascular Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China., Guo J; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Center of Cerebrovascular Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China., Guo H; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China., Zhang X; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Center of Cerebrovascular Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China., Fan J; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Center of Cerebrovascular Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China., Zhang K; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Center of Cerebrovascular Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China., Mao J; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. maojunj@mail.sysu.edu.cn.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. maojunj@mail.sysu.edu.cn.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. maojunj@mail.sysu.edu.cn., Zhou B; Center of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. zhoub2@mail.sysu.edu.cn.; Institute of Interventional Radiology, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. zhoub2@mail.sysu.edu.cn.; Center of Cerebrovascular Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. zhoub2@mail.sysu.edu.cn.; Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China. zhoub2@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of nanobiotechnology [J Nanobiotechnology] 2024 Jun 18; Vol. 22 (1), pp. 338. Date of Electronic Publication: 2024 Jun 18.
DOI: 10.1186/s12951-024-02579-1
Abstrakt: Background: Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely linked to the development of a tumor immunosuppressive environment (TIME). In this study, underlying mechanisms and potential therapeutic targets involved in the formation of TIME in residual tumors following iRFA were explored. Then, TAK-981-loaded nanocomposite hydrogel was constructed, and its therapeutic effects on residual tumors were investigated.
Results: This study reveals that the upregulation of small ubiquitin-like modifier 2 (Sumo2) and activated SUMOylation is intricately tied to immunosuppression in residual tumors post-iRFA. Both knockdown of Sumo2 and inhibiting SUMOylation with TAK-981 activate IFN-1 signaling in HCC cells, thereby promoting dendritic cell maturation. Herein, we propose an injectable PDLLA-PEG-PDLLA (PLEL) nanocomposite hydrogel which incorporates self-assembled TAK-981 and BSA nanoparticles for complementary localized treatment of residual tumor after iRFA. The sustained release of TAK-981 from this hydrogel curbs the expansion of residual tumors and notably stimulates the dendritic cell and cytotoxic lymphocyte-mediated antitumor immune response in residual tumors while maintaining biosafety. Furthermore, the treatment with TAK-981 nanocomposite hydrogel resulted in a widespread elevation in PD-L1 levels. Combining TAK-981 nanocomposite hydrogel with PD-L1 blockade therapy synergistically eradicates residual tumors and suppresses distant tumors.
Conclusions: These findings underscore the potential of the TAK-981-based strategy as an effective therapy to enhance RFA therapy for HCC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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