| The inducement of liver cancer is very complex.It is generally believed that it is related to drinking,viral hepatitis,poisons,genetic factors,parasites and so on.The common feature of liver cancer is that it can cause persistent inflammatory damage in the liver.This kind of persistent inflammation will lead to the damage and death of hepatocytes,which will lead to the fibrosis of hepatocytes,leading to a large area of necrosis and death,which is particularly important for the treatment of liver cancer.A recent study shows that toll like receptor 4(TLR4)can promote the growth of liver cancer,and the activation of TLR4 pathway will mainly cause a strong and rapid inflammatory immune response.Can we inhibit the growth of liver tumor by inhibiting the expression of TLR4 pathway,reducing the release of inflammatory factors and reducing the inflammation of liver.At present,there are not many TLR4 inhibitors that can be widely used,most of them have strong toxic and side effects,and many traditional natural Chinese medicines have anti-inflammatory and anti-inflammatory effects,so we think that we can select several effective ingredients in traditional natural Chinese medicine as TLR4 inhibitors.In this study,TLR4 inhibitors were selected from the effective components of natural Chinese medicine,and a kind of(glycyrrhizic acid,GA)was selected as the representative,which was supported by poly(L-glutamic acid)grafted poly(ethylene glycol)/ m-aminophenylboronic acid(PLG-g-m PEG / PBA),then nano particles(GANPs)were prepared and injected into tail vein.In this paper,the H22 in situ tumor model of liver cancer was established,and a series of cell and animal experiments were carried out to explore the therapeutic effect and safety of the effective components of natural Chinese medicine represented by GA-NPs on liver cancer.To prepare a kind of polymer carrier which can carry the effective components of natural Chinese medicine,through consulting the literature,to find out the possible TLR4 inhibitor of the effective components of natural Chinese medicine,to select some of them for cell experiment in vitro to verify their effect,to select one as the representative to prepare nanoparticles,and to conduct basic drug characterization.To construct H22 hepatocarcinoma in situ tumor model,set up different treatment groups(PBS,small molecule treatment group,nanoparticles treatment group),and evaluate the therapeutic effect of drugs by statistics of mice weight,survival rate,tumor quality and other data.Nine effective components of natural Chinese medicine with the potential to inhibit TLR4 pathway were screened: glycyrrhizic acid,baicalin,puerarin,phenethyl caffeic acid,quercetin,tannic acid,epigallocatechin gallate,dihydromyricetin and chlorogenic acid.GA-NPs was successfully prepared.The drug characterization was as follows: the drug loading was 18.3%,the average hydrodynamic radius of GA-NPs was 125 nm and the distribution width was 0.19 by Malvern particle size detector.PLG-gm PEG/PBA is nontoxic in cell MTT test.GA-NPs is nontoxic in low concentration,but low in high concentration.IC50 of GA-NPs is 846.563?g/ml.There was no death in the maximum tolerance MTD experiment of mice under the high dose of Free-GA of 100 mg / kg,and the survival time was higher than 30 days.When the concentration of GA-NPs was 50 mg / kg(calculated on the basis of GA),the tumor inhibition results of H22 hepatocarcinoma in situ model: compared with the tumor mass of PBS group,Free-GA group and GA-NPs group could significantly inhibit tumor growth(P < 0.0001),compared with Free-GA group,GA-NPs group could significantly inhibit tumor growth(P < 0.00171849)The nine active components of natural Chinese medicine have the inhibitory effect on TLR4.GA NPs polymer nanoparticles were successfully prepared.GA NPs has low toxicity to cells in high dose,and is not toxic to mice in a certain concentration range(about 2g/kg).GA NPs can play a significant anti-tumor role in H22 hepatocarcinoma in situ model... |
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