| Nano preparations have broad application prospects in terms of"attenuating and enhancing efficacy"of traditional antitumor chemotherapy drugs.Glycogen,an energy storage substance in animals,has good biocompatibility and degradability in vivo.Glycogen is a highly branched glucan with natural spherical dendritic nanostructures and is an ideal drug nanocarrier material.In this thesis,an anti-tumor drug carrier with active targeting and environmental response and a tumor chemotherapy-photothermotherapy combined therapy drug carrier are developed through structural modification and surface modification of glycogen nanoparticles.The specific content is as follows:(1)Glycogen-based pH-Sensitive liver cancer tumor targeting nano-drug carriersThis chapter investigates a multifunctional nanocarrier based on glycogen nanoparticles for cancer treatment.Glycogen nanoparticles(Glycogen,Gly)are combined with hepatoma cell-targeting agent?-galactose(Galactose,Gal)sugar and anticancer drug doxorubicin (Doxorubicin,DOX)through a Schiff base reaction to form a nano-drug loading system(Gly-DOX-Gal).NMR,UV,IR and other analytical methods were used to confirm its structure.The diameter of the obtained nanoparticles was about 70 nm.The in vitro release results showed that the drug release rate of Gly-DOX-Gal reached 53.89%at pH 5.0,which was much higher than 16.48%the normal physiological environment pH 7.4.Through in vitro protein adsorption experiments,degradation experiments,and stability experiments,glycogen nanocarriers have the advantages of good biocompatibility,stability,and long circulation in vivo.Due to galactose-ASGPR binding,glycogen nanocarriers can be selectively taken up by liver cancer cells.After endocytosis,the drug was released from the nanoparticles due to the cleavage of Schiff base bonds in the acidic tumor cell environment.Cell experiments show that nanoparticles have no obvious toxicity to normal cells and have good inhibitory effect on cancer cells.Animal experiments show that the glycogen-based drug delivery system can minimize the absorption and drug leakage of normal organs,and have low toxicity to normal tissues and organs,in addition it can improve the drug in tumor sites,and have good tumor inhibition effect.Therefore,glycogen nanoparticles have good advantages as anticancer drug carriers.(2)Glycogen-based chemotherapy-photothermotherapy combined therapy nanocarrierBased on the previous chapter,glycogen nanoparticles in this chapter are oxidized and coupled with the anticancer drug doxorubicin through a disulfide bond(-ss-),and polymerize polypyrrole nanoparticles(ppy)with photothermal effect in situ.A functional phospholipid layer(Lipid-RGD)is wrapped around to form the Gly-ss-DOX@ppy@Lipid-RGD system.Under 2W/cm~2(5 min)near-infrared irradiation,the nanocarrier can be heated to 52°C.In vitro drug release test,we found that the phospholipid layer can reduce drug leakage by nanoparticles and promote drug release.The drug release under near-infrared irradiation at 10mmol/L glutathione concentration can reach 82%,which is much higher than 59%without near-infrared irradiation,indicating that the photothermal effect can promote the release of carrier drugs.Cell experiments have shown that the drug-loading system has lower cytotoxicity to normal cells,and the combined effect of chemotherapy and photothermotherapy under near-infrared light irradiation is far better than that of chemical medicine alone,showing good tumor suppressive effect and tumor targeting.In vivo experiments,the results show that nanocarriers have lower damage to normal tissues and organs.Also polypyrrole nanoparticles can absorb near-infrared light and radiate thermal energy in tumors.To enhance drug release and provide photothermal treatment for tumors and finally suppress tumor growth.The above results show that Gly-ss-DOX@ppy@Lipid-RGD has good advantages as a nanocarrier for targeting liver cancer. |
PDF Full Text Request