Abstract
In addition to early detection, early diagnosis, and early surgery, it is of great significance to use new strategies for the treatment of hepatocellular carcinoma (HCC). Studies showed that the combination of sorafenib (SFN) and triptolide (TPL) could reduce the clinical dose of SFN and maintain good anti-HCC effect. But the solubility of SFN and TPL in water is low and both drugs have certain toxicity. Therefore, we constructed a biomimetic nanosystem based on cancer cell-platelet (PLT) hybrid membrane camouflage to co-deliver SFN and TPL taking advantage of PLT membrane with long circulation functions and tumor cell membrane with homologous targeting. The biomimetic nanosystem, SFN and TPL loaded cancer cell-PLT hybrid membrane-camouflaged liquid crystalline lipid nanoparticles ((SFN + TPL)@CPLCNPs), could simultaneously load SFN and TPL at the molar ratio of SFN to TPL close to 10:1. (SFN + TPL)@CPLCNPs achieved long circulation function and tumor targeting at the same time, promoting tumor cell apoptosis, inhibiting tumor growth, and achieving a better "synergy and attenuation effect", which provided new ideas for the treatment of HCC.Graphical
Highlights
Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers
To realize long circulation and homologous tumor targeting of the nanoparticles, (SFN + TPL)@ LCNPs were camouflaged with cancer cell-PLT hybrid membrane
As observed by the transmission electron microscope (TEM) (Fig. 1a), the prepared (SFN + TPL)@LCNPs and (SFN + TPL)@cell-PLT hybrid membrane-camouflaged LCNPs (CPLCNPs) were spherical in shape with good monodispersity
Summary
Introduction Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. HCC can be treated by surgical resection, liver transplantation, liver-oriented therapy, and systemic chemotherapy. Among these treatment strategies, only surgical resection and liver transplantation are considered as potentially possible cures. Based on our previous study and predecessors’ research, we found that the combination of sorafenib (SFN) and triptolide (TPL) had shown synergistic effects on HCC [3]. We fused PLT membrane with Huh-7 cell (human liver cancer cell line) membrane and fabricated SFN and TPL loaded cancer cell-PLT hybrid membrane-camouflaged liquid crystalline lipid nanoparticles. We designed (SFN + TPL)@CPLCNPs to co-encapsulate SFN and TPL for a synergistic anti-tumor effect. The anti-tumor activity of (SFN + TPL)@CPLCNPs and its mechanisms were investigated in vitro and in vivo
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