Tao Ran,Wang Chengzhang,Zhang Changwei,Li Wenjun,Zhou Hao,Chen Hongxia,Ye Jianzhong
Hepatocellular carcinoma (HCC) is one of the most lethal diseases worldwide. Ginkgo Biloba Leaves polyprenol (GBP) is considered potential efficacy in the treatment of HCC. This study involved oil-in-water type nanoemulsion (NE) loading GBP and Fullerene C60 (C60F)
were prepared by dissolving GBP and C60F in NE using inversed phase emulsification (EIP) with ultrasonic-assisted emulsification (UAE) method. Folic acid (FA) coupled Chitosan (CS) and Graphene oxide (GO) nanocomposites (NCs): FA-CS-GO-NCs were fabricated by ionic cross-linking
of positively charged FA-CS-GO solution conjugates and negative charged NE with TPP. We combined these materials for preparing NCs loading GBP and C60F (GBP-C60F-FA-CS-GO-NCs) based GBP-C60F-NE. GBP-C60F-FA-CS-GO-NCs in the NE were the mean size
was 44.9 nm, PdI was 0.267 and the mean zeta potential was 47.8 mV. And they had good drug loading efficiency, encapsulation efficiency, drug release property and storage stability. In this cytotoxic study, it demonstrated the GBP-C60F-FA-CS-GO-NCs were greater inhibition capacity
on MHCC97H cells compared with GBP-NE, C60F-NE, GBP-C60F-NE, GBP-FA-CS-GO-NCs and C60F-FA-CS-GO-NCs. In this genotoxic study, GBP-C60F-FA-CS-GO-NCs at low C60F concentration showed low genotoxicity on MHCC97H and L02 cells. By comparison,
GBP-C60F-FA-CS-GO-NCs had higher cytotoxicity on MHCC97H than L02 cells. By the cell apoptosis analysis, the results revealed that GBP-C60F-NE and GBP-C60F-FA-CS-GO-NCs could obviously induce MHCC97H cell apoptosis, especially high concentration GBP-C60F-FA-CS-GO-NCs
had the strongest apoptosis inducing ability. The treatment against MHCC97H cells with moderate C60F concentrations of GBP-C60F-FA-CS-GO-NCs effectively inhibited the overexpressions of Akt1 and Akt2, and significantly increased the expression of PTEN. Our results suggest
that PTEN, Akt1 and Akt2 might play an important role in the aspect of GBP-C60F-FA-CS-GO-NCs inhibiting against HCC cells. It provides further evidence to speculation that up-regulated PTEN expression and down-regulated Akt1 and Akt2 expression might be one of the important mechanisms
for GBP-C60F-FA-CS-GO-NCs inhibiting HCC cells. All these results suggest that GBP-C60F-FA-CS-GO-NCs effectively inhibited the HCC malignant development and has potentially important value in the HCC treatment.
Ran Tao,Chengzhang Wang,Yin Lu,Changwei Zhang,Hao Zhou,Hongxia Chen,WenJun Li
Background This study demonstrated an innovative formulation including the polyprenol (GBP) lipid and vitamin E-TPGS hybrid nanoparticles (NPs) which was aimed to control the transfer of betulinic acid (BA) and low-substituted hydroxyl fullerenol (C60(OH)n). Additionally, it developed BA-C60(OH)n-GBP-TPGS-NPs delivery system and researched the anti-hepatocellular carcinoma (HCC) effects.Materials and Methods The NPs were prepared by nanoprecipitation with ultrasonic-assisted emulsification (UAE) method. It was characterized by scanning electronic microscopy (SEM), transmission electron microscopy (TEM), FTIR spectrum, size distribution and zeta potential. Physical and chemical properties were evaluated through measurement of drug release, stability studies, drug loading efficiency (DE) and encapsulation efficiency (EE). Biological activities were evaluated through measurement of MTT assay, lactate dehydrogenase leakage assay (LDH), cell proliferation assays, cell apoptosis analysis, comet assay, wound healing assay, cell invasion and Western blot analysis.Results and Conclusions The NPs exhibited clear distribution characteristics, improved solubility and stability. BA and C60(OH)n for the NPs displayed a biphasic release pattern with sustained drug release properties. The mixture of C60(OH)n with different hydroxyl groups may have a certain effect on the stability of the NPs system itself. The NPs could effectively inhibit MHCC97H cell proliferation, migration and invasion in vitro. Combined use of C60(OH)n and BA in GBP lipids may improve the inhibit effect of C60(OH)n or BA against HCC cells and reduce cytotoxicity and genotoxicity of C60(OH)n for normal cells. We concluded that one of the important mechanisms of BA-C60(OH)n-GBP-TPGS-NPs inhibiting MHCC97H cells is achieved by up-regulating the expression of Caspase-3, Caspase-8 and Caspase-9.
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