A Comparative Study On The Construction Of Paclitaxel-targeted Nanoparticles Based On Dopamine Self-polymerization And Chemical Synthesis

Background:The conventional chemical synthetic method refers to the polymer carrier material immobilized ligand molecules targeting carrier material or directly connect the drug carrier material at one terminal through a series of covalent reaction,although this way more mature but time-consuming,low production rate,extraction and purification step and multifarious process.what's worse,synthetic polymer materials may lose their original properties and the quality of the drug loading.Objective:In this study,folate-modified paclitaxel nanoparticles were prepared by polydopamine method and chemical synthesis method,and the properties and anti-tumor effects of the targeted nanoparticles by these two different methods were investigated to compare.Methods:PTX-PDA-FA nanoparticles were obtained by using the method of dopamine polymerization.Dopamine hydrochloride was placed under alkaline conditions,and the surface of nanoparticles was oxidized and self-polymerized to form a thin layer of polydopamine(PDA).PTX-FA nanoparticles were prepared by chemical synthesis of polymer carrier materials coupled with folic acid and high pressure homogenization by anti-solvent precipitation.Dynamic light scattering method,transmission electron microscopy method were adopted to investigate two kinds of nanoparticles size and morphology.Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were used to verify the successful conjugations of polydopamine and folic acid.HPLC method was employed to determine drug loadings content and the immobilized folic acid amount.The stability in physiological medium,hemolytic and drug release profiles of the targeted nanoparticles in vitro were determined.The cytotoxicity of two kinds of nanoparticles was evaluated by MTT method on 4T1,HeLa cells,and anti-tumor activity was investigated using Balb/C mice bearing 4T1 breast cancer.Results:The nanoparticles prepared by the two methods were rod-shaped,and the PTX-PDA-FA nanoparticles prepared by the polydopamine method had smaller particle size.The two nanoparticles were stable in 5%glucose and rat plasma.There was no hemolysis phenomenon.In vitro drug release behavior represented sustained slow release profiles,which conformed with the zero-order release dynamics model.The MTT results showed that both PTX-PDA-FA NPs and PTX-FANPs showed significantly enhanced and equivalent targeted inhibitory effects compared with the folate-free nanoparticle group.In vivo anti-tumor results showed that both folate-loaded nanoparticles had higher tumor growth inhibitory effects,and the differences between them were not significant.Furthermore,compared with paclitaxel injection,the mice treated with nanoparticles groups kept vigorous and activation,diminished weight loss and reduced systemic toxicity.Conclusion:Targeted nanoparticles prepared by polydopamine method can achieve similar superior anti-tumor activity comparable to that of the chemical synthesis method in vivo and in vitro,simultaneously alleviated severe side effects.Compared with the targeted nanoparticles prepared by chemical synthesis,the PDA coating nanoparticles don't need to use organic solvent,without removing impurity,purification these cumbersome steps,which indicated that is a more facile and effective surface functionalization methods,and has the great potential targeted tumor therapy on nanoscale delivery system in the future.