Construction Of Transferrin Curcumin Nanoparticles By Acid Denaturation And Its Tumor Targeting

Because the molecular weight of the drug is small,only a small part can be applied to the tumor site,the drug can not distinguish between normal tissue and tumor tissue and has toxic side effects on the human body,which becomes an important factor limiting and hindering the efficacy of the drug,so the nano-targeted tumor The research of the drug system has become a hot spot to solve this problem.The drug-loaded nanoparticles prepared by transferrin can not only significantly improve the water solubility of the hydrophobic drug,but also specifically localize to the tumor site due to binding to the transferrin receptor,and reduce the toxicity of the antitumor drug.Curcumin is an acidic polyphenolic substance extracted from the rhizome of Zingiberaceae.It has low toxicity and broad pharmacological effects.Curcumin has anti-inflammatory and anti-oxidation effects and inhibits the proliferation and metastasis of tumor cells[1-2]However,its poor water solubility,low bioavailability,and low concentration in serum and tissues make its half-life short and metabolism too rapid[3-4]Transferrin is an excellent nanoparticle carrier that non-toxic and nonimmunogenic.Transferrin(transferrin,Tf)is a single-chain glycoprotein widely distributed in human blood,containing 679 amino acid residues,38 cys,forming 19 pairs of disulfide bonds,and transferrin disulfide bonds to its receptor makes an important impact.Transferrin not only participates in the transport and metabolism of iron ions,but also regulates iron ion balance and energy balance[5].Due to the large demand for iron ions in tumor cell growth and proliferation,the transferrin receptor is lowly expressed on the surface of normal human cells,and the number of TfR on the surface of tumor cells is 2 to 7 times that of normal cells.Transferrin binds to the transferrin receptor(TfR),and the binding rate of TfR to Tf on the surface of tumor cells is 10 to 100 times that of normal cells[6].The transferrin-related preparation can rapidly accumulate and remain in the tumor site,and the therapeutic drug is specifically transported into the tumor cell through the active targeting of the transferrin and transferrin receptor transport pathway(TF-TfR).Thereby exerting efficacy[7].Transferrin can be prepared as a complex with drugs,polymers,and liposomes.Firstly,the transferrin blank nanoparticles were prepared by using the characteristics of transferrin.During the formation of nanoparticles,the fluorescence intensity of the protein gradually weakened and the surface hydrophobic region decreased.We speculated that the hydrophobic region plays an important role in the assembly process of transferrin effect.On the basis of preparation of transferrin nanoparticles,self-assembly of transferrin-loaded nanoparticles was carried out.Electron microscopy showed that the prepared nanoparticles had spherical particles of about 40-160 nm,and the UVspectrophotometer and protein quantitative detection of curcumin had a maximum drug loading of up to 22.7%.In vitro Tf-CCM nanoparticle in vitro targeting experiments,laser scanning confocal microscopy revealed that most of the Tf-CCM nanoparticles aggregated in the cytoplasm of tumor cells.In the NIR-797 near-infrared nanoparticle-bearing mice,it was found that Tf-CCM can accumulate in the tumor site,indicating that Tf-CCM nanoparticles have good targeting to tumor tissues,which are curcumin nanoparticles.Further research lays a foundation.At last,compatation was did to the metabolites of MCF-7 adiministered by CCM and Tf-CCM by Metabonomics method and found that Glycerophospholipid metabolism is the main acess of CCM and Tf-CCM.The group of CCM effect the cell accesses of Pantothenate and Co A biosynthesis,Valine,leucine and isoleucine biosynthesis,Glycine,serine and threonine metabolism;While the group of CCM effect the cell accesses of Arginine and proline metabolism,Phenylalanine metabolism.The differences and similarities to the mechanism of action of MCF-7 for CCM and TfCCM could be found by Metabonomics method.And foundation could be laid to a deeper mechanism research.