Design And Study Of Multifunctional Anti-protein Adsorption Polymer Nano-drug Carrier

With the continuous innovation of science and technology,multi-functional anti-protein adsorption polymer nanodrug carriers have made vigorous development,especially in the active targeted delivery of anticancer drugs,enhancement of tumor therapy and viral neutralization therapy,and other fields have made remarkable progress,opening up the possibility of nano drug carrier in vivo therapy.Nano-drug carriers are able to interact with biological macromolecules in the serum to form a "protein corona" on its surface,which not only blocks the targeting ability of the nanoparticles,but also makes them easy to be recognized and cleared by phagocytes.Although more and more antifouling materials have been developed,they still face great challenges in achieving completely "protein-free" and targeted transport as anti-protein adsorbed nanomaterials.On the other hand,in December 2019,the novel coronavirus pneumonia(COVID-19),caused by Severe acute respiratory syndrome Coronavirus 2(SARS-Co V-2),broke out worldwide.Although the novel coronavirus vaccine and specific drugs have achieved initial results,their high production cost,expensive price and toxic side effects still lead to many deficiencies in the field of novel coronavirus treatment.In this paper,two anti-protein adsorption nanodrug carriers with different functions were designed for targeted cancer therapy and neutralization therapy of novel coronavirus.Specific work is as follows:(1)Design of self-polishing polymer nanoparticles with antifouling performance and targeted group protectionIn this chapter,a new thermosensitive self-polishing antifouling α-amylase-starch nanoparticles coated with polymethyl methacrylate were designed,and the nanoparticles were doped with aptamers and photodynamic therapeutic drugs to prepare α-ams-SCMMA-TPPOHApt NPs.This kind of nanoparticles can protect the targeted groups in the nucleus when stored at 20 ℃ or lower temperature.When the temperature is raised to body temperature(37 ℃),the shell hydrolase can be triggered to hydrolyze the inner shell of polysaccharide.By using the concept of self-polishing,the "protein corona" of surface adsorption can be completely eliminated,the targeted groups can be exposed,and drugs can be delivered to the target docking site.Self-polishing nanoparticles have excellent anti-protein adsorption ability and complete protein corona free performance.Meanwhile,when loaded with photodynamic drugs and coupled aptamer,they can not only have high targeting efficiency,but also release singlet oxygen to achieve the effect of cancer treatment,which has an ideal application prospect.(2)Design of polymer-coated nanoparticles with the neutralization ability of novel coronavirusIn this chapter,we designed a polymer nanoparticle coated by alveolar epithelial cell membrane with the ability to neutralize and compete with the novel coronavirus.Firstly,the cell membrane of human type II alveolar epithelium was extracted and purified by high-speed differential centrifugation,and then the cell membrane vesicles were mixed with PLGA nanoparticles by Avanti small extruder and continuously extruded to obtain PLGA NPs@ATIIM,and then SCMMA NPs were prepared by emulsion polymerization process.And conjugates S1 protein to simulate the novel coronavirus SCMMA NPs-S1.PLGA NPs@ATII-M has good anti-protein adsorption ability,and also has a very strong binding ability with S1 protein,can play a good virus neutralization and competition effect.Compared with traditional vaccine prevention or drug therapy,the virus neutralization nanoparticles designed in this subject have short production cycle,low cost,easy stable preservation,strong neutralization competitiveness,and have good application prospects in the field of virus neutralization therapy.