Study On Dual-Targeted Poly(Ether-Ester)Magnetic Micelle With Different Shapes For Cancer Treatment

At present,accurate and highly efficient delivery of chemotherapy drugs with nanocarriers to tumor site for achieving excellent therapeutic efficacy still remains a major challenge in cancer chemotherapy,which causing more and more scholars concern.Copolymer micelle nanocarriers with magnetic targeting and active targeting of the rod-shaped bacteria shape can achieve long circulating in the blood effectively,enhancing the accumulation of drug in tumor site and reducing normal tissue toxicity.Therefore,considering the combination of active targeting and magnetic targeting with rod-like shape which is similar with bacteria,we can construct a double targeting nanocarriers,which can be used in the field of drug delivery.In this thesis,we first synthesized PBA-PEG-PCL and mPEG-PCL copolymer materials.The rod-like shape micelles Ri,R₂ were prepared by adding 0.05M NaCl solution during the micelle preparation process,while the formation of spherical-like micelles S₁,S₂ were without adding NaCl solution.And the shape and size of the micelles were investigated by DLS?CLSM?TEM.The rod-like architecture with diameter?20 nm and length?600 nm and the spherical-like architecture with diameter?110 nm.To study the stability of the prepared micelles within 120 h in 0.9%in NaCl solution,we can find that the average particle size of the micelles and particle size distribution does not change,shows that the micelles have good stability.The biocompatibility of the prepared micelles was investigated,and the spherical and rod-like micelles showed good biocompatibility.In vitro inhibition of tumor growth results showed that drug-loaded micelles are able to inhibit the proliferation of A549/HepG2 cells,and the PBA active targeting with rod-like shape R₂@DOX had the best effect.The cell uptake efficiency A549/HepG2 to different shape micelles was evaluated,which can be found that rod-like shape micelles were more easily uptaken by tumor cell,what's more,the material modified with small molecule ligands strengthen the combination of receptor and ligand,the rod-like shape and the multivalent binding prompted the cellular uptake.Finally,we established the mouse hepatoma H22 tumor model in BALB/C mice to investigate the inhibition of tumor growth in vivo.Pharmacokinetic results show that rod-like shape micelle compared to spherical-like shape has longer circulation time in blood;the rod-like shape drug-loaded micelles with active target and magnetic target makes the concentration of DOX increased significantly in tumor site,and in other normal tissues the concentration of DOX have the least enrichment.At the end of the 21 d after treatment,for the R₂@DOX/Fe₃O₄ group,mice weight loss is not obvious,the tumor volume and tumor weight are minimum,tumor proliferation is the slowest.Histological analysis also found that the group could obviously induce apoptosis of tumor cells,it was further proved that the inhibition of tumor cell growth was the most prominent.