Research On The Antitumor Effect Of BH3 Delivered By Gold Nanoparticles

Cancer has always been one of the main causes of disease death in most countries,and it is a serious threat to human health.Surgery,radiotherapy,and chemotherapy are common treatments for cancer.However,both surgery and radiotherapy have no therapeutic effect on the occurrence of potential metastatic lesions,but only on the treatment of local tumors;although chemotherapy is a systemic treatment method,its drug targeting is poor,the side effects are high,and the drug is selective Low,the treatment effect is often lacking.In order to solve the shortcomings of the above treatment methods,nanomedicine came out.Although nanomedicine has the advantages of strong targeting,prolonged drug half-life and increased drug loading,it will still cause more side effects after entering the body,which cannot effectively achieve the safe treatment effect of malignant tumors Research is still an important research directionIn this paper,based on the role of the lethal domain of Bcl-2 family proteins,BH3-only protein,in cell apoptosis,a section of BH3 small-molecule peptide monomer(abbreviated as BH3)with a sequence of Asp-Ala-Ser-Thr-Lys-Lys-Leu-Ser-Glu-Cys-Leu-Arg-Arg-Ile-Gly-Asp-Glu-Leu-Asp-Ser-Pra.BH3 binds to pro-survival proteins in Bcl-2 family proteins,leading to the failure of pro-survival proteins,which in turn promotes the role of apoptotic members and promotes programmed cell death.However,BH3,like other biologically active macromolecules,has the disadvantages of low cell membrane permeability,poor stability against proteolysis,and low endosome escape rate.Therefore,with the help of nanocarriers,BH3 can be delivered into tumor cells to play a role.In this paperBH3 gold nanoparticle drug systems with different coating ratios were successfully constructed,and examples of drug systems with higher loading efficiency were selected by HPLC method,referred to as BH3@AuNPs-1 and BH3@AuNPs-2 for short.The synthesized nano-drug system was characterized by ultraviolet-visible spectroscopy scanning,particle size and Zeta potential measurement,and infrared spectroscopy analysis,which initially confirmed the successful synthesis of the delivery systemWe evaluated the antitumor effect and mechanism of nanomedicine at the cellular level.First,the MTT experiment was used to compare AuNPs carrier and BH3 small molecule peptide monomer with no cytotoxicity.BH3@AuNPs-1 and BH3@AuNPs-2 nano drugs have high cytotoxicity,indicating that AuNPs drug carrier can effectively co-load small molecules The peptide enters the cell.Has a good anti-tumor effect.The anti-tumor effects of BH3@AuNPs-1 and BH3@AuNPs-2 delivery systems were initially verified by colony formation experiments and dye rejection experiments.Flow cytometry found that there were more cells in the early and late stages of apoptosis under the effect of the delivery system,indicating that the BH3@AuNPs-1 and BH3@AuNPs-2 delivery systems have the effect of promoting tumor cell apoptosis.Through the cell scratch test,it was found that under the action of the BH3@AuNPs-1 and BH3@AuNPs-2 delivery systems,the cells had poor healing ability and weak cell invasion ability,indicating that BH3@AuNPs-1 and BH3@AuNPs-2 delivery system has the effect of inhibiting tumor cell migration and infiltration.By measuring the change of mitochondrial membrane potential and the change of Caspase-3/-8/-9 gene activity in A549 cells,it was found that the mitochondrial membrane potential of cells under the action of BH3@AuNPs-1 and BH3@AuNPs-2 delivery system decreased,Caspase-3/-8/-9 gene activity increased,indicating that the delivery system can not only promote cell apoptosis through endogenous pathways,but also promote cell apoptosis through exogenous pathways.