Studies On Antioxidant Activity Of Water-soluble Fullerene Nanoparticles And Their Construction As Tumor Targeting Drug Delivery System

In the past two decades,with the development and progress of nano-science and technology,the development of functional nanomaterials has made rapid progress,and has played an unprecedented role in the field of biomedicine.Fullerene and its derivatives have been the focus of research since their discovery,due to their unique properties and potential application prospects,and have shown potential application value in many fields,such as drug transport,biological imaging and photodynamic therapy.Based on this,after surface hydrophilic modification of fullerene,the antioxidant activity of water-soluble fullerene nanoparticles was studied by measuring its scavenging ability to free radicals and anti-lipid peroxidation.Using water-soluble fullerene nanoparticles as the carrier,loading the drug curcumin?CUR?with antioxidant and anti-tumor effects,a novel tumor-targeted drug delivery system was constructed to achieve targeted modification of water-soluble fullerene nanoparticles and efficient loading of hydrophobic drugs.The main contents and results of this thesis are as follows.?1?Water-soluble small molecule tri-tetraethylene glycol?TEG?and fullerene were self-assembled into water-soluble fullerene nanoparticles C₆₀-TEGs,and their antioxidant capacity was determined by improved DPPH method.The results showed that 1 mg different types of water-soluble fullerene nanoparticles could absorb about 4 mg DPPH radicals,respectively.The oxygen radical scavenging ability of water-soluble fullerene nanoparticles was determined by ORAC method,the results showed that the ORAC value of water-soluble fullerene nanoparticles was about 23 times that of vitamin C,which has good oxidation resistance.?2?The antioxidant drug curcumin?CUR?was loaded on C₆₀-TEGs nanoparticles by thin film dispersion to obtain CUR/C₆₀-TEGs antioxidant drug nanocarrier system.The highest encapsulation efficiency could reach 93.5%and the maximum amount of adsorption CUR was 6.25%.The anti-lipid peroxidation activity of CUR/C₆₀-TEGs nano-loaded system was evaluated by studying the inhibitory effect of CUR/C₆₀-TEGs nano-loaded system on lipid peroxidation in FeCl₂ and ascorbic acid induced liver homogenates of rats.The results showed that CUR/C₆₀-TEGs nanoparticles the anti-lipid peroxidation was significantly enhanced compared with curcumin alone in DMSO solution due to the fullerene nanoparticles C₆₀-TEGs but also the ability to scavenge hydroxyl radicals.CUR/C₆₀-TEGs nanoparticles were co-cultured HepG-2 human hepatoma cells and their cytotoxicity was studied.The results showed that the highest inhibition rate was87.5%after 48 h of HepG-2 culture of drug-loaded nanoparticles and human hepatoma cells,which indicated that CUR/C₆₀-TEGs nanoparticles could effectively inhibit the proliferation of hepatoma cells and significantly improve the CUR resistance hepatocytoma activity?P<0.05?,while fullerene nanoparticles without drug loading C₆₀-TEGs hardly cause cell damage and have good biocompatibility.?3?Targeting small molecule folate?FA?was covalently modified on the surface of C60-TEGs nanoparticles by linking hydrophilic block polymers?H2N-PEG-NH2?to construct C60-TEGs-PEG-FA tumor targeting carriers and characterize their structures.The CUR was further loaded onto C60-TEGs-PEG-FA nanoparticles by physical adsorption to construct CUR/C60-TEGs-PEG-FA targeted nanomedicine delivery system,transmission electron microscopy?TEM?and dynamic state light scattering?DLS?results show that the average particle size was 95±1.8 nm,and the particle size distribution was uniform.the results of in vitro drug release experiments showed that the release curve of CUR/C60-TEGs-PEG-FA nanomedicine delivery system became gentle after 24 h of drug release,indicating that the targeted nanomedicine delivery system had obvious sustained release effect.The anti-tumor cell proliferation of nanoparticles was studied by classical CCK-8 method in vitro.The results showed that CUR/C60-TEGs-PEG-FA could effectively target FR highly expressed human luminal epithelial carcinoma KB cells,compared with the non-target group CUR/C60-TEGs have a more obvious inhibitory effect on the growth and proliferation of cancer cells.To sum up,using the good antioxidant properties of water-soluble fullerene nanoparticles,a novel antioxidant drug nanopharmaceutical delivery system was constructed.The experimental results showed that it could improve the bioavailability and antioxidant activity of water-insoluble antioxidant drugs.Then a novel tumor-targeted drug delivery system was constructed with water-soluble fullerene nanoparticles modified by targeting.The experimental results showed that the targeted carrier has good biocompatibility,drug-loading performance and targeting,and has a good application prospect in targeted therapy of tumor.