期刊
NANOSCALE RESEARCH LETTERS
卷 15, 期 1, 页码 -出版社
SPRINGER
DOI: 10.1186/s11671-020-03451-5
关键词
Glypican-3; Hepatocellular carcinoma; Targeted therapy; Wnt signal
资金
- National Natural Science Fund of China [82071862, 81872017, 81572431]
- Anhui Provincial Science and Technology program [202004j07020053]
- University Natural Science Research Project of Anhui Province [KJ2018ZD011]
- R&D project of Wuhu Research Institute of Anhui University of Science Technology [ALW2020YF17]
- Huainan Science and Technology Project [2017B41]
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.
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