Preparation Of Polypeptide Zwitterionic Materials And Its Application In Anticancer Drug Delivery System

Zwitterionic polymers have been playing an increasingly important character in the field of nanobiomedicine,due to their excellent nonfouling properties.However,the traditional zwitterionic polymers based on phosphorylcholine,sulfobetaine,and carboxybetaine cannot be degraded by human body.Polypeptide,the component of protein has excellent biocompatibility and can be degraded by the human body.In this thesis,we combined zwitterions with polypeptide,and prepared a series of zwitterionic polymers based on polypeptide.Then we investigate their applications as anti-cancer drug delivery system.The main contents and conclusions of this thesis were described as below:1.Amphiphilic block copolymer based on polypeptide was synthesized by NCA ring-opening method.The synthesized amphiphilic block copolymer can self-assemble into micelles with a zwitterionic shell and a hydrophobic core.The zwitterioinc shell endow the micelles nonfouling properties,and the results of in vitro experiments showed that the cytotoxicity and cell uptake of DOX was decreased when DOX was encapsulated into zwitterionic polypeptide micelles.We can change the ratio of the hydrophilic part and hydrophobic part to accommodate the size of the micelles,to make the micelles accumulate in tumor tissue via EPR effect.2.An amphiphilic block copolymer composed of glutamic acid(E),lysine(K)and phenylalanine(F)was prepared by condensation polymerization and NCA ring-opening polymerization.In the aqueous solution,it can self-assemble into micelles with a zwitterionic shell(E/K=1/1)and a hydrophobic core(phenylalanine).3.A DOX loaded vesicle with high drug loading efficiency and high drug loading content was prepared by combining DOX with polypeptide composed of glutamic acid(E)and lysine(K)with a ratio of 1/1.The drug-loaded vesicles were stable in physiological environment and FBS environment,but the loaded drug can be rapidly released under low pH and enzyme conditions.The endocytosis and toxicity of the vesicles was enhanced by further modification with RGD.4.Hydrogels composed of equally mixed L-glutamic acid(E)and L-lysine(K)polypeptide after crosslinked by the coupling reaction between carboxyl groups and primary amines catalyzed by 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide·HCl(EDC-HCl),were prepared to improve biocompatibility through reducing the nonspecific protein adsorption and cell attachment.Two model drugs,doxorubicin hydrochloride(DOX·HCl)(positively charged anti-cancer drug),and diclofenac sodium(negatively charged anti-inflammatory drug),loaded hydrogels showed accelerated complete drug release and full enzymatic degradation in the presence of trypsin,which was reported to be expressed in various carcinomas and inflammations.