hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway
Abstract Delivery of tumor-specific inhibitors is a challenge in cancer treatment. Antibody-modified nanoparticles can deliver their loaded drugs to tumor cells that overexpress specific tumor-associated antigens. Here, we constructed sorafenib-loaded polyethylene glycol-b-PLGA polymer nanoparticles...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-11-01
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| Series: | Nanoscale Research Letters |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s11671-020-03451-5 |
| _version_ | 1797713152942538752 |
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| author | Jing Shen Wenpeng Cai Yongfang Ma Ruyue Xu Zhen Huo Li Song Xinyin Qiu Yinci Zhang Amin Li Weiya Cao Shuping Zhou Xiaolong Tang |
| author_facet | Jing Shen Wenpeng Cai Yongfang Ma Ruyue Xu Zhen Huo Li Song Xinyin Qiu Yinci Zhang Amin Li Weiya Cao Shuping Zhou Xiaolong Tang |
| author_sort | Jing Shen |
| collection | DOAJ |
| description | Abstract Delivery of tumor-specific inhibitors is a challenge in cancer treatment. Antibody-modified nanoparticles can deliver their loaded drugs to tumor cells that overexpress specific tumor-associated antigens. Here, we constructed sorafenib-loaded polyethylene glycol-b-PLGA polymer nanoparticles modified with antibody hGC33 to glypican-3 (GPC3 +), a membrane protein overexpressed in hepatocellular carcinoma. We found that hGC33-modified NPs (hGC33-SFB-NP) targeted GPC3+ hepatocellular carcinoma (HCC) cells by specifically binding to GPC3 on the surface of HCC cells, inhibited Wnt-induced signal transduction, and inhibited HCC cells in G0/1 by down-regulating cyclin D1 expression, thus attenuating HCC cell migration by inhibiting epithelial–mesenchymal transition. hGC33-SFB-NP inhibited the migration, cycle progression, and proliferation of HCC cells by inhibiting the Ras/Raf/MAPK pathway and the Wnt pathway in tandem with GPC3 molecules, respectively. hGC33-SFB-NP inhibited the growth of liver cancer in vivo and improved the survival rate of tumor-bearing mice. We conclude that hGC33 increases the targeting of SFB-NP to HCC cells. hGC33-SFB-NP synergistically inhibits the progression of HCC by blocking the Wnt pathway and the Ras/Raf/MAPK pathway. |
| first_indexed | 2024-03-12T07:32:02Z |
| format | Article |
| id | doaj.art-7563b89e2ad84e8dac4277099e4314b0 |
| institution | Directory Open Access Journal |
| issn | 1556-276X |
| language | English |
| last_indexed | 2024-03-12T07:32:02Z |
| publishDate | 2020-11-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Nanoscale Research Letters |
| spelling | doaj.art-7563b89e2ad84e8dac4277099e4314b02023-09-02T21:44:18ZengSpringerOpenNanoscale Research Letters1556-276X2020-11-0115111510.1186/s11671-020-03451-5hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling PathwayJing Shen0Wenpeng Cai1Yongfang Ma2Ruyue Xu3Zhen Huo4Li Song5Xinyin Qiu6Yinci Zhang7Amin Li8Weiya Cao9Shuping Zhou10Xiaolong Tang11Medical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyMedical School, Anhui University of Science and TechnologyWuhu Research Institute, Anhui University of Science and TechnologyAbstract Delivery of tumor-specific inhibitors is a challenge in cancer treatment. Antibody-modified nanoparticles can deliver their loaded drugs to tumor cells that overexpress specific tumor-associated antigens. Here, we constructed sorafenib-loaded polyethylene glycol-b-PLGA polymer nanoparticles modified with antibody hGC33 to glypican-3 (GPC3 +), a membrane protein overexpressed in hepatocellular carcinoma. We found that hGC33-modified NPs (hGC33-SFB-NP) targeted GPC3+ hepatocellular carcinoma (HCC) cells by specifically binding to GPC3 on the surface of HCC cells, inhibited Wnt-induced signal transduction, and inhibited HCC cells in G0/1 by down-regulating cyclin D1 expression, thus attenuating HCC cell migration by inhibiting epithelial–mesenchymal transition. hGC33-SFB-NP inhibited the migration, cycle progression, and proliferation of HCC cells by inhibiting the Ras/Raf/MAPK pathway and the Wnt pathway in tandem with GPC3 molecules, respectively. hGC33-SFB-NP inhibited the growth of liver cancer in vivo and improved the survival rate of tumor-bearing mice. We conclude that hGC33 increases the targeting of SFB-NP to HCC cells. hGC33-SFB-NP synergistically inhibits the progression of HCC by blocking the Wnt pathway and the Ras/Raf/MAPK pathway.http://link.springer.com/article/10.1186/s11671-020-03451-5Glypican-3Hepatocellular carcinomaTargeted therapyWnt signal |
| spellingShingle | Jing Shen Wenpeng Cai Yongfang Ma Ruyue Xu Zhen Huo Li Song Xinyin Qiu Yinci Zhang Amin Li Weiya Cao Shuping Zhou Xiaolong Tang hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway Nanoscale Research Letters Glypican-3 Hepatocellular carcinoma Targeted therapy Wnt signal |
| title | hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway |
| title_full | hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway |
| title_fullStr | hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway |
| title_full_unstemmed | hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway |
| title_short | hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway |
| title_sort | hgc33 modified and sorafenib loaded nanoparticles have a synergistic anti hepatoma effect by inhibiting wnt signaling pathway |
| topic | Glypican-3 Hepatocellular carcinoma Targeted therapy Wnt signal |
| url | http://link.springer.com/article/10.1186/s11671-020-03451-5 |
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