The Design And Preparation Of 10-hydroxycamptothecin Drug Carrier And Its Anti-tumor Activity In Vitro

Recently,cancer has become one of the main killers of human health.As a product integrating nanotechnology and biochemical technology,nanomedicine carrier plays an important role in the treatment of cancer.The nano drug carrier can not only improve the solubility and bioavailability of the hydrophobic drug,but also increase the drug concentration of the tumor site through targeted delivery.Responsive releasing of the drug can be achieved by the response of carrier to special substances in tumor microenvironment.10-hydroxycamptothecin(HCPT),one of camptothecin derivative,is a broad-spectrum anticancer drug.Due to its inherent structural characteristics,the solubility of HCPT is poor,which limited its application.In this paper,a graft polymer-cytotoxin prodrug,where a potent anticancer drug HCPT and water-soluble methoxypolyethylene glycols(mPEG)were attached into the polyester backbone,was synthesized via thiol-ene reaction.The prepared graft polymer-HCPT prodrug could be self-assembled into nanosized micelles(ca.153 nm)in aqueous solution,which were uniform and stable.We performed a series of characterizations of micelles and explored their antitumor activity in vitro.In addition,considering the drug resistance caused by single drug in the treatment,we adopt a new idea that choosing molybdenum sulfide nanosheet with photothermal conversion ability as a drug carrier.HCPT was connected to molybdenum sulfide through covalent bond.We carried out a series of studies on the properties of the carrier.Based on the above content,we mainly did the following work:(1)Maleic anhydride and ethylene glycol was used to synthesis polyester which can be degraded by esterase.The polyester was used as skeleton of the polymer.The hydrophilic mPEG and hydrophobic was attached to polyester through the addition reaction of sulfhydryl group and double bond.The amphiphilic graft copolymer prodrug is then self-assembled into stable polymer micelles in water.The polymer micelles have a uniform particle size and good stability.The HCPT loading is up to 20.4%.The micelles have a sensitive esterase responsiveness.MTT experiments confirmed that the polymer micelles synthesized have good anti-tumor activity in vitro,which provides a reference for the study of hydrophobic drugs in polymer prodrugs and esterase-responsive polymer drug carriers.(2)Molybdenum sulfide nanosheets with a particle size of about 200 nm were prepared by hydrothermal method and ultrasonic mechanical stripping method.The mPEG modified by lipoic acid(LA)were connected to Molybdenum sulfide nanosheets by covalent bond.HCPT is connected to the molybdenum sulfide nanosheet by covalent bond too.Finally,we obtained a stable molybdenum sulfide carrier system that combined photothermal and chemotherapy.