Gambogic Acid Loaded Polymeric Micelles Improve Therapeutic Effect In Breast Cancer

Cancer is one of the most serious human health problems in the world,and the mortality rate shows an increasing trend every year.The cancer problem deserves everyone’s attention.Gambogic acid（GA）has been proven to have potent anti-tumor activity in a variety of tumors,its mechanism of action mainly involves the induction of tumor cell apoptosis,inhibition of tumor cell proliferation,anti-tumor cell metastasis,inhibition of channel protein activity,reversal of multidrug resistance of tumor cells and many other aspects.However,the poor water solubility of GA limits its clinical transformation and utilization.In recent years,rapid development of nanotechnology has provided us with a solution to overcome drug solubility problems.In our work,MPEG-PCL polymer micelles were designed by us,which can efficiently encapsulate GA to form GA loaded MPEG-PCL polymeric micelles（GA micelles）for the treatment of tumors.The main contents of this paper’s research are:Synthesis and characterization of the drug carrier MPEG-PCL:MPEG-PCL was prepared by ring-opening polymerization using the parent drug,and the structure of MPEG-PCL was identified by ¹H NMR spectroscopy;Formulation of GA micelles:The particle size,dispersion coefficient（PDI）,encapsulation efficiency,and drug loading were used as indices to examine the effect of different prescription conditions on GA micelles and determine the best prescription;Study on the quality of GA micelles:Focusing on the content of GA micelles,entrapment efficiency,drug loading,particle size,potential,and in vitro release behavior;In vitro antitumor activity of GA micelles:cultured tumor cells were treated with different concentrations of gambogic acid in dimethyl sulfoxide and GA micelles,and a drug-free culture negative control was set.MTT method was used to test the inhibition rate of cell proliferation after 24h and 48h of drug treatment.SPSS software was used to fit the curve of cell proliferation rate,and the half inhibition concentration(IC₅₀)of each group was calculated by using Annexin V-FITC/PI double staining.Apoptosis was detected by apoptosis assay,and GA uptake in GA micelles was detected by HPLC;in vivo antitumor activity of GA micelles.Through experiments proved:The GA micelles showed small average particle size（29±2 nm）,high encapsulation efficiency（92.06±0.03%）,and sustained drug releasebehavior in vitro.Compared to free GA,GA micelles showed superior aqueous dispersity in water,higher tumor cellular uptake,enhanced cytotoxicity of GA and apoptosis induction effect against MCF-7 cells.Furthermore,in vivo studies in MCF-7subcutaneous xenograft models demonstrated GA micelles showed better antitumor effect than free GA.Histopathological analysis of Ki-67 and TUNEL staining further demonstrated that GA micelles could significantly suppress proliferation and increase apoptosis of tumor cells.Inconclusion,wehave prepared MPEG-PCL polymer-encapsulated GA nano-micelle to improve the therapeutic effect of breast cancer.