Preparation Of Polydopamine Targeting Nanoparticles And Their Anti-tumor Research

At present,surface modification of targeted nanoparticles faces enormous challenges.Traditional surface modification requires that the polymer carrier must have a reactive functional group in order to chemically couple the carrier to the targeting ligand.The process is cumbersome and the drug carrier may lose its drug loading capacity after chemical modification,resulting in failure of nanoparticle preparation.To overcome this problem,we have adopted a new surface modification method,polydopamine(PDA)method.The principle is that dopamine can self-assemble into PDA in an alkaline environment and form a film on the surface of the nanoparticles.Since the PDA itself has a large number of reactive functional groups,it is possible to further link the targeting ligand.The method is simple to operate(stirring and incubation)and does not require the carrier to have a reactive functional group,which is universal.This topic is intended to study the application of polydopamine in drug delivery systems:(1)Firstly,doxorubicin(DOX)nanoparticles were prepared by double emulsion method,and then PDA was coated on the surface and connected with folic acid FA and RGD peptides to prepare DOX-PDA-FA-NPs and DOX-PDA-RGD-NPs(targeted nanoparticles).Subsequently,by measuring the particle size,potential,TEM,XPS etc.,we found that the particle size of the two targeted nanoparticles was small(190.91±0.19,194.97±1.33 nm)and shape of them was spherical The two targetred nanoparticles can be stably present in various physiological media,and exhibits pH sensitivity in drug release.At the same time,we also demonstrated the successful connection between FA and RGD and the PDA layer on the nanoparticles.Targeted nanoparticles have better targeting ability to HeLa cells compared to DOX-NP nanoparticles:in vivo studies have shown that tumor-targeting rates of targeted nanoparticles are more than 70%,while significantly reducing the side effects of DOX and increasing drug distribution in mouse tumors.(2)Traditional chemical coupling methods and PDA methods are two widely used methods for the preparation of targeted nanoparticles.This article aims to compare the effects of these two different preparation methods on the antitumor effect.FA-PDA-DOX liposomes was prepared by PDA method and DOX-FA liposomes was prepared by traditional chemical methods.The particle size of FA-PDA-DOX liposomes was slightly larger than that of DOX-FA liposomes,but both of them had higher stability and showed strong cytotoxicity to HeLa cells(0.91 ±0.19 vs 0.68±0.13 μg/mL)and high drug accumulation at the tumor site.However,only FA-PDA-DOX liposomes showed pH-sensitive properties,which may be attributed to the fact that the PDA layer was destroyed under acidic conditions to peel off the surface of the liposome.This study showed that FA-PDA-DOX liposomes(70.40%)had similar antitumor effects compared to DOX-FA liposomes(76.90%),and FA-PDA-DOX liposomes were safer than DOX-FA liposomes.In summary,this paper proves that the PDA method is an effective new tumor-targeted treatment strategy.The nanoparticle prepared by the PDA method is simpler in process,safer in effect,and can achieve a similar therapeutic level as the nanoparticle prepared by the conventional method.The PDA method has a good treatment prospect,and provides another possibility for the clinical application of nano drug delivery system in the future.