Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation
Abstract Objective To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC), and explore the underlying mechanism. Materials and Methods...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Nanobiotechnology |
| Online Access: | https://doi.org/10.1186/s12951-023-02170-0 |
| _version_ | 1797397814965174272 |
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| author | Yanyan Cao Tao Sun Bo Sun Guilin Zhang Jiayun Liu Bin Liang Chuansheng Zheng Xuefeng Kan |
| author_facet | Yanyan Cao Tao Sun Bo Sun Guilin Zhang Jiayun Liu Bin Liang Chuansheng Zheng Xuefeng Kan |
| author_sort | Yanyan Cao |
| collection | DOAJ |
| description | Abstract Objective To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC), and explore the underlying mechanism. Materials and Methods The effect of OK-432 and lyOK-432 was compared in activating dendritic cells (DCs). RADA16-I (R) peptide was dissolved in a mixture of lyOK-432 (O) and DOX (D) to develop an ROD hydrogel. The characteristics of ROD hydrogel were evaluated. Tumor response and mice survival were measured after different treatments. The number of immune cells and cytokine levels were measured, and the activation of cGAS/STING/IFN-I signaling pathway in DC was evaluated both in vitro and in vivo. Results LyOK-432 was more effective than OK-432 in promoting DC maturation and activating the IFN-I pathway. ROD was an injectable hydrogel for effectively loading lyOK-432 and DOX, and presented the controlled-release property. ROD treatment achieved the highest tumor necrosis rate (p < 0.001) and the longest survival time (p < 0.001) compared with the other therapies. The ROD group also displayed the highest percentages of DCs, CD4+ T cells and CD8+ T cells (p < 0.001), the lowest level of Treg cells (p < 0.001), and the highest expression levels of IFN-γ and TNF-α (p < 0.001) compared with the other groups. The expression levels of pSTING, pIRF3, and IFN-β in DCs were obviously higher after treatment of lyOK-432 in combination with DOX than the other therapies. The surviving mice in the ROD group showed a growth inhibition of rechallenged subcutaneous tumor. Conclusion The novel ROD peptide hydrogel induced an antitumor immunity by activating the STING pathway, which was effective for treating residual liver cancer after iRFA of HCC. |
| first_indexed | 2024-03-09T01:15:38Z |
| format | Article |
| id | doaj.art-67a424ac04034bd495e0c15ed2aff4b9 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-09T01:15:38Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-67a424ac04034bd495e0c15ed2aff4b92023-12-10T12:30:27ZengBMCJournal of Nanobiotechnology1477-31552023-11-0121111510.1186/s12951-023-02170-0Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablationYanyan Cao0Tao Sun1Bo Sun2Guilin Zhang3Jiayun Liu4Bin Liang5Chuansheng Zheng6Xuefeng Kan7Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Objective To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC), and explore the underlying mechanism. Materials and Methods The effect of OK-432 and lyOK-432 was compared in activating dendritic cells (DCs). RADA16-I (R) peptide was dissolved in a mixture of lyOK-432 (O) and DOX (D) to develop an ROD hydrogel. The characteristics of ROD hydrogel were evaluated. Tumor response and mice survival were measured after different treatments. The number of immune cells and cytokine levels were measured, and the activation of cGAS/STING/IFN-I signaling pathway in DC was evaluated both in vitro and in vivo. Results LyOK-432 was more effective than OK-432 in promoting DC maturation and activating the IFN-I pathway. ROD was an injectable hydrogel for effectively loading lyOK-432 and DOX, and presented the controlled-release property. ROD treatment achieved the highest tumor necrosis rate (p < 0.001) and the longest survival time (p < 0.001) compared with the other therapies. The ROD group also displayed the highest percentages of DCs, CD4+ T cells and CD8+ T cells (p < 0.001), the lowest level of Treg cells (p < 0.001), and the highest expression levels of IFN-γ and TNF-α (p < 0.001) compared with the other groups. The expression levels of pSTING, pIRF3, and IFN-β in DCs were obviously higher after treatment of lyOK-432 in combination with DOX than the other therapies. The surviving mice in the ROD group showed a growth inhibition of rechallenged subcutaneous tumor. Conclusion The novel ROD peptide hydrogel induced an antitumor immunity by activating the STING pathway, which was effective for treating residual liver cancer after iRFA of HCC.https://doi.org/10.1186/s12951-023-02170-0 |
| spellingShingle | Yanyan Cao Tao Sun Bo Sun Guilin Zhang Jiayun Liu Bin Liang Chuansheng Zheng Xuefeng Kan Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation Journal of Nanobiotechnology |
| title | Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation |
| title_full | Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation |
| title_fullStr | Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation |
| title_full_unstemmed | Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation |
| title_short | Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation |
| title_sort | injectable hydrogel loaded with lysed ok 432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation |
| url | https://doi.org/10.1186/s12951-023-02170-0 |
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