Synthesisand Biological Propertiesresearchs Of Two Different Drug-loaded Polyrotaxanes

For a long time,Cancer treatment is regarded as a worldwide problem.Chemotherapy commonly used in clinic is often accompanied by severe toxic and side effects.The low solubility of anti-cancer drugs and the multi-drug resistance of cancer cells make chemotherapy less effective and easy to relapse after initial treatment.So one of the key challenges for cancer therapy is to develop chemotherapeutic agents,that can passively or actively target to eliminate cancer cells without damaging the surrounding tissues.In recent years,nanomaterials have become more and more widely used in the biological field,especially in cancer treatment and diagnosis.Nanomaterials constructed by the supramolecular chemistry break the limitations of traditional covalent bond chemical building materials and have attracted extensive attention.Cyclodextrin is a nontoxic natural product,and has good biocompatibility.It is one of the host molecules of supramolecular chemistry.CDs can be threaded onto a proper linear polymermolecule under the driving of non-covalent bond,forming the pseudopolyrotaxane and then polyrotaxane can beobtained by capping the pseudopolyrotaxane with bulky end-caps.Compared with the traditional organic nanomaterials,the cyclodextrin polyrotaxane has a unique chemical structure,good biocompatible,is easy to chemically modify and the cyclodextrin can migrate on the polymer axis,so that it is easy to penetrate in tumor tissues.Therefore,it has a good application prospect in the field of drug delivery.At present,there are a lot of reports about polyalkane,which end-capped with different macromolecular groupin the medical field.However,the use of the porphyrin terminated cyclodextrin polyanes has not yet been reported.The four pyrrole rings are composed of the porphyrin,which is a highly conjugated macrocyclic system,that acts as anticancer agents and antibiotics to increase phototoxicity and kill cancer cells.At the same time,porphyrins can be used as fluorescent agents to track the distribution of nanomaterials in vivo.In this paper,we report two types of a-cyclodextrin polyrotaxanes based on a-CD and dicarboxyl-PEG(Mn?4200).Then water soluble and specific modifications were carried out.And the anticancer drugs were loaded through different methods.Finally,their biological properties were studied by in vitro and in vivo experiments.The specific research contents are as follows:1?Two kinds of polyalkanes with alpha-CD as the main body and the dicarboxyl-PEG(Mn?4200)as the object were synthesized by the amidation reaction.The two polyanes were terminated with(6-amino-6-O)-P-cyclodextrin(P-CD-NH2)and 5-(4-Aminophenyl)-10,15,20-triphenylporphyrin(mATPP)as end-capping agent.The structures and morphologies of the two polyrotaxanes were characterized by 1HNMR,X-ray powder diffractionand transmission electron microscopy.2.The specificity and water solubility of P-CD-NH2 and mATPP-terminated a-cyclodextrin polyrotaxane were modified by the use of d-alpha-tocopheryl polyethylene glycol succinate(TPGS)and succinic anhydride,respectively.Then the two anticancer drugs 10-hydroxycamptothecin and cisplatin were loaded onto two a-cyclodextrin polyrotaxanes,the drug loadings were about 7.1%and 6.9%,respectively.And then we studied the drug release,cell uptake,and anti-tumor activity in vitro and in vivo of the two drug-loaded polyrotaxanes.The results show that camptothecin can release effective drugs through ester bonds in the presence of esterase.At the same time,cisplatin can release cisplatin from the ligand loaded cisplatin in the acid environment and maintain its original efficacy,and the drug carrying polyamothane has a good antitumor effect.It has a good application prospect in the field of biology.