Antitumor And Immunomodulatory Effects Of Liver Targeting Curcumin/polysaccharide PLGA Nanoparticles

Curcumin(Cur)is a diketone compound in the Zingiberaceae,which is mainly used for food staining.In recent years,scientists have found that curcumin also has anti-inflammatory,anti-tumor,anti-oxidation,and lipid-lowering effects.In terms of its anti-cancer properties,recent studies have proved that curcumin can exert anti-cancer effects by inducing the apoptosis of tumor cells and inhibiting tumor cell growth stages.But curcumin itself is insoluble in water,and its properties are very unstable and easy to degrade by light and high temperatures.Therefore,in recent years,many scientists have tried to use nanotechnology to improve curcumin properties and make it more convenient for clinical research.PLGA(polylactic acid glycolic acid),as a degradable polymer organic compound,has been widely used in nanomaterial research.Nano-sized materials can improve the bioavailability of the coated drug,improve the stability of the drug,realize sustained drug release in vivo,and can be targeted at cancer cells by passive targeting in vivo.It is an excellent drug delivery carrier.In recent years,polysaccharides have become a hot subject in immunity.More and more natural polysaccharides are extracted from plants or fungi.Natural polysaccharides have extensive immunomodulatory effects,usually through immune-related cell regulation.Recently,fungal sulfated polysaccharides extracted from algae have antioxidant,anti-tumor and anti-virus effects.Generally,we think of polysaccharides on tumor inhibitory effect is not caused by direct effects on tumor,but as the role of immune regulator function in the body’s immune cells such as increase of T and B lymphocytes and NK the tumor cell killing effect on natural killer cells,improve the phagocytosis of macrophages,and the secretion of cytokines to inhibit tumor.The first chapter of this paper introduces the tumor and its treatment methods.It introduces the advantages of natural drugs compared with traditional chemotherapy drugs,and the anti-tumor mechanism of natural drugs in many aspects.The application advantages of PLGA as a carrier of nanomaterials,the research overview of PLGA as a carrier of drug delivery,and the research background and significance of this paper are discussed in this paper.The second chapter of this paper examines the advantages and problems of curcumin and fucosum polysaccharide as anticancer agents.PLGA is modified with lactose acid to target liver cancer.PLGA-Cur-Lac and PLGA-FUC nanoparticles are synthesized by the emulsified solvent evaporation method,and their characterization and related physical and chemical properties are verified.It was proved that both were microspheres with a particle size of about 200 nm.These microspheres could be uniformly dispersed in water,and slowly degrade and release drugs under acidic conditions.Curcumin,in particular,not only improves the problem of its hydrophobic nature and difficult to use.It also enables it to have both active and passive targeting functions for liver cancer.Both bioavailability was greatly improved.By spectrophotometric method,curcumin drug loading was 4.8%,and ROCK-algae polysaccharide drug loading was 7.4%.In the third chapter,the antitumor activity and tumor cell targeting of PLGA-Cur-Lac in vitro were studied using mouse hepatocellular carcinoma cells Hepa1-6 as a model.It can be seen from the results that PLGA-Cur-Lac,compared with free curcumin,does not need to be prepared into suspension first,and can be directly dissolved in culture medium and treated with a filtration membrane before administration.Moreover,PLGA-Cur-Lac has a better inhibitory effect on HEPA1-6,significantly promotes tumor cell apoptosis,and has a lower IC50 value than free curcumin.At the concentration of 20 μg/m L,the inhibitory effect on cells was significantly better than that of free drug administration,which may be due to the improvement of stability,so that it is not easy to degrade in the medium,so it still plays a critical role at low concentrations.Because curcumin has its own fluorescence,the fluorescence intensity of free CUR,PLGA-Cur and PLGA-Cur-Lac was observed directly by a fluorescence microscope.The fluorescence intensity of curcumin nanoparticles with targets was higher,indicating that the nanoparticles had targeting properties.In the fourth chapter,the effects of PLGA-FUC and Fuc on phagocytosis activity,NO release and cytokine secretion of macrophages were investigated using RAW264.7mouse mononuclear macrophages as a model.Studies have found that both PLGA-FUC and Fuc can effectively activate macrophages,increase macrophage phagocytic activity,increase the release of NO,TNF-α and IL-6 secretion.This indicates that PLGA-FUC can activate macrophages and has certain immune regulatory properties,making it a more stable immune enhancer.In Chapter 5,the experimental results of PLGA curcumin and polysaccharide nanoparticles were summarized and then suggests further scientific and technical issues to be addressed in this field.