The Studies On Preparation And Antitumor Activity Of Water-soluble Conjugated Polymer Polyphenylene Ethynylene Nanoparticles Containing Oligonucleotides

Artificially synthesized CpG oligodeoxynucleotide(CpG ODN)can imitate immune enhancement of bacterial DNA.Therefore,Artificially synthesized CpG ODN can be used as therapeutic DNA and immune adjuvant enhancer.Since unmodified CpG ODN can be readily degraded by the enzymes in the organism and was difficult to be uptaken by tumer cells,repeated high-dose drug administration was required in disease treatment.In this paper,cationic water-soluble conjugated polymer polyphenylene ethynylene(PPE)nanoparticles were synthesized,and PPE nanoparticles can not only delivered CpG nucleic acid molecules by electrostatic interaction,but also had good biocompatibility and fluorescence stability.Therefore,it can be used as an ideal gene carrier.In this paper,the new-fashioned PPE gene vector was used for loading CpG ODN,studied on characterization of structure and properties,biocompatibility and anti-tumor effect.The main research work is as follows:(1)PPE nanoparticles were prepared by the method of Sonagashira.The structure of PPE nanoparticles were confirmed and characterized by nuclear magnetic resonance;The morphology of PPE nanoparticles were characterized by transmission electron microscope;The Photophysics properties of PPE nanoparticles were analyzed by ultraviolet spectrophotometer and fluorescence spectrophotometer.Determination of PPE nanoparticles particle size and zeta potential by dynamic light scattering method.The average hydrodynamic diameter of the PPE nanoparticles was 275.1±3.1 nm,the PDI was 0.196±0.138,and zeta potential was 41.7±3.6 mV.(2)Studied on the assembly behavior of PPE and CpG,and researched on the structure and properties of PPE-CpG ODN architecture.It was shown that CpG ODN forms stable architecture with PPE nanoparticles at N/P ratios above 2/1(PPE to CpG ODN)by particle size and zeta potential measurements.(3)The biocompatibility of PPE nanoparticles were determined by MTT method.The results showed that PPE nanoparticles had good biocompatibility.(4)Established the tumor-bearing mice model to evaluate the tumor therapeutic effect of PPE-CpG ODN architectures.The results showed that PPE-CpG ODN architectures can play a better role in antitumor than CpG ODN.In conclusion,PPE nanoparticles through electrostatic interactions could delivery CpG ODN efficiently for antitumer.