Design And Properties Of Stimuli Responsive Biomedical Materials Based On Ganoderma Lucidum Polysaccharide

In recent years,with the interdisciplinary development of biology,chemistry,and materials,stimuli responsive biomedical materials that integrate multiple functions have been widely used in the fields of drug delivery,tissue engineering,medical devices,and biosensors.Among many biomedical materials,natural polysaccharides have attracted much attention due to their good biocompatibility,degradability,safety and other advantages.Ganoderma Lucidum polysaccharide(GLP)is one of the main active ingredients of the traditional precious Chinese medicinal material Ganoderma lucidum which is usually used directly as medicine or participates in adjuvant therapy in traditional medicine.GLP is a heteropolysaccharide composed of a variety of monosaccharides.The main monosaccharide component is glucose.Its molecular chain has a large number of hydroxyl groups and has excellent chemical reaction performance.Moreover,GLP also has immune regulation,antiinflammatory,hypoglycemic,anti-viral,anti-tumor and other biological activites,so it is a kind of potential biomedical material frameword material.In this work,GLP was used as the framework material to design and construct a variety of stimuli responsive biomedical materials,including nano drug delivery systems for tumor treatment and hydrogel sensors that can be used for physiological signal monitoring.The specific research contents are as follows:The construction of Ganoderma lucidum polysaccharide-betulinic acid(GLP-BA)antitumor nano-drug delivery system based on EPR effect and its anti-tumor performance in vitro and in vivo.GLP with anti-tumor properties was used as the hydrophilic backbone,an amphiphilic GLP-BA macromolecular prodrug was synthesized through esterification to make it self-assemble and encapsulate the second anti-tumor drug 10-hydroxycamptocamptoid(HCPT).The drug-loaded nanoparticles(GLP-BA/HCPT)composed of natural compounds with passive targeting effect were prepared.GLPBA/HCPT nanoparticles have a suitable particle size(~122 nm)and a high drug loading capacity(HCPT: 21.3%).Cell experiments show that GLP has a certain inhibitory effect on tumor cells.GLP-BA/HCPT nanoparticles promote the uptake ability of tumor cells to drugs(2.4 times that of pure drugs),and the two anti-tumor drugs loaded in GLP-BA nanoparticles can exert a good synergistic effect(synergistic index CI = 0.81),and have good anti-tumor properties in vitro and in vivo(the relative tumor inhibition rate reached 67.04% after 14 days of treatment).In addition,after the nanoparticle administration treatment,the weight,the number of white blood cells in the blood and the Ig E level of the mice were not abnormal.Construction of p H-responsive GLP anti-tumor nano drug delivery system and research on its anti-tumor performance in vitro and in vivo.According to the unique slightly acidic environment of the tumor tissue,the 1,3-diol structure on the GLP molecular chain and the anti-tumor drug methotrexate(MTX)are connected by a borate bond with 3-aminophenylboronic acid(APBA).A p H-stimuli responsive release nano drug delivery system(GLP-APBA-MTX/HCPT)was prepared.The particle size of GLP-APBAMTX/HCPT nanoparticles is about 190 nm,and the borate ester bond can be broken under the stimulation of slightly acidic environment to release anti-tumor drugs.The release of MTX and HCPT at p H 6.5 is 1.9 and 1.4 times higher than that at p H 7.4,respectively.Cell experiments show that the nanoparticles could promote the accumulation of HCPT in tumor cells.After treatment for the same time,the amount of HCPT loaded in cells is three times that of pure drug.The excellent stimuli responsive drug release properties of GLP-APBAMTX/HCPT nanoparticles exhibit significant anti-tumor properties in vitro and in vivo.Construction and preparation of a multi-drug programmed release GLP-based nanodrug delivery system with p H/GSH dual response and research on its anti-tumor performance in vitro and in vivo.In order to further improve the intelligence of the nano drug delivery system,a GLP nano-drug delivery system(RCGDDH)with a dual response of p H and glutathione(GSH)that can simultaneously regulate the tumor microenvironment and play a therapeutic role has been constructed.Firstly,rutin and double hydrogen artemisinin(DHA)respectively by boric acid ester and glutathione(GSH)response of disulfide bond connected with GLP,HCPT is loaded and encapsulated in nanoparticles through self-assembly.The loaded three drugs can achieve programmed release in tumor tissues.RCGDDH nanoparticles have more suitable particle size(~98 nm)and high drug contents(6.1% rutin,12.5% DHA,28.3% HCPT).In vitro release experiments have shown that the borate bond can be broken in the slightly acidic environment of tumor tissue firstly,and then disulfide bond can be broken in the high GSH environment in tumor cells.Under p H 5.2 and 10 m M GSH conditions,HCPT and DHA released by nanoparticles were 2.5times and 2.7 times higher than those under normal physiological conditions,respectively.In addition,the first release rutin can effectively inhibit the activity of matrix metalloproteinase MMP-9,regulate the tumor microenvironment,thereby reducing tumor infiltration and metastasis.Preparation and performance study of Ganoderma lucidum polysaccharide intelligent conductive hydrogel loaded with MXene.According to the feature that the adjacent diol structure on the GLP molecular chain can interact with the borate bond,the tannic acid modified MXene nanosheet(TA-MXene)was introduced into the cross-linking system of GLP and polyvinyl alcohol(PVA)to construct a TA-MXene-GLP/PVA hydrogel strain sensor with good electrical conductivity.GLP gives the hydrogel excellent tensile properties,and TA-MXene makes it have good mechanical properties,electrical conductivity and strain sensing properties.The elongation at break of TA-MXene-GLP/PVA hydrogel can reach2370%,and it can complete 96.9% self-repair after 15 min.Tannic acid enables the hydrogel to exhibit good adhesion properties on various materials such as wood,glass and skin.In addition,the hydrogel has a good electrical conductivity and a high sensing sensitivity(GF= 2.67),which can identify small movements such as swallowing and writing,and perform signal output.The prepared TA-MXene-GLP/PVA hydrogel has potential application value in a variety of biomedical materials such as electronic skin and physiological signal monitoring devices.In summary,this thesis uses the biological activity and chemical reactivity of Ganoderma lucidum polysaccharides to construct a variety of stimuli responsive intelligent biomedical materials,which provides ideas for the development and utilization of Ganoderma lucidum polysaccharides in the field of biomedical field,and also has reference significance for the high value utilization of similar bioactive polysaccharides.