Tumor Microenvironment-sensitive Polyurethane Micelles For Triggered Intracellular Drug Delivery For Osteosarcoma Treatment

Objective: At present,the clinical effect of chemotherapy for osteosarcoma is still not satisfactory.Multidrug resistance and toxic side effects remain the main problems of chemotherapy.In this paper,we attempted to prepare a drug carrier system,which can be called polyethylene glycol(PEG)shielded reduction sensitive polyurethane nanomicelles,as a drug carrier to overcome the above two problems of chemotherapy.Methods: In the first chapter,we summarized the recent progress in the treatment of osteosarcoma,and the problems of Doxorubcin chemotherapy: drug multidrug resistance and cardiotoxicity,and the progress of reversing these problems.The application progress of nano drug delivery system in reversing doxorubicin toxicity and multidrug resistance was reviewed,and the research ideas of this subject were put forward.The first part of the paper introduces the preparation and properties of drug controlled release polyurethane nanomicelles,which are divided into three sections.The first section reviews the research progress of polymeric micelles.The second section introduces the reduction sensitive polyurethane nano micelle preparation method for the reducible PEG shielding,containing the drug release of the adriamycin micelles in the cells,the biocompatibility of the micelles,and the antitumor experiment in vitro.The third section summarizes the results of the experiment.The micelle preparation experiments show that:(1)the size of the micelles is very small,and it is stable under normal physiological conditions,and it can circulate in the human body for a long time,which is beneficial to the release of drugs.(2)micelles have redox sensitivity,which can rapidly escape from hydrophilic shell micelles and release doxorubicin rapidly.Polymeric micelles have good biocompatibility and biodegradability.The second part of the article introduces the drug controlled release polyurethane nano micelles for the treatment of osteosarcoma,which is divided into four sections.In the first section,the pharmacokinetic experiments of drug loaded micelles were introduced to determine the changes in the concentration of free adriamycin and adriamycin in inbred ICR mice(ICR)mice after single intravenous administration.In the second section,the experimental results of pharmacokinetics were summarized.Through the adriamycin phar The first part of the paper introduces the preparation and properties of drug controlled release polyurethane nanomicelles,which are divided into three sections.The first section reviews the research progress of polymeric micelles.The second section introduces the reduction sensitive polyurethane nano micelle preparation method for the reducible PEG shielding,containing the drug release of the adriamycin micelles in the cells,the biocompatibility of the micelles,and the antitumor experiment in vitro.The third section summarizes the results of the experiment.The micelle preparation experiments show that:(1)the size of the micelles is very small,and it is stable under normal physiological conditions,and it can circulate in the human body for a long time,which is beneficial to the release of drugs.(2)micelles have redox sensitivity,which can rapidly escape from hydrophilic shell micelles and release doxorubicin rapidly.Polymeric micelles have good biocompatibility and biodegradability.macokinetics experiments of different groups,free adriamycin,adriamycin SS-PU-SS-PEG group and adriamycin SS-PU-b-PEG showed obvious three-phase clearance curve,and the last two types of adriamycin clearance curves were always located in the free opiate.On the basis of mycin,the process of blood clearance was delayed and the half-life of blood was prolonged.The third section describes the inhibitory effect of adriamycin on the growth of sarcoma osteogenic(SAOS2)in nude mice.By measuring the volume and weight of the tumor and weight of the SAOS2 nude mice after the administration,the inhibitory effect of adriamycin on the tumor and the side effects on the body were observed.The results of the fourth section of adriamycin on the growth inhibition of SAOS2 nude mice showed that free adriamycin and two drug adriamycin groups had obvious tumor growth inhibition,the tumor weight and volume decreased obviously,and the tumor weight and tumor volume in the free adriamycin group and the SS-PU-b-PEG group were the same as that of the tumor volume.The two groups were close to the growth inhibition of the tumor,while the tumor weight,volume and tumor suppressor rate of the SS-PU-SS-PEG group were significantly lower than that of the free adriamycin group and the SS-PU-b-PEG group.The tumor suppressor effect was obviously better than the previous two kinds of drug delivery methods.Results: This study successfully prepared the polyurethane nano micelles with a controlled release of drug in cells.In vitro experiments proved that the polymer micelles have good biocompatibility,and have reduction sensitivity,which can release the drug in the cell quickly.It can delay the blood clearance of adriamycin,prolong the blood half-life,and inhibit the growth of osteosarcoma.Conclusion: The fourth chapter makes a summary of this paper,The reduction of sensitivity to PEG shielding polyurethane(SS-PU-SS-PEG)micelles is a good drug carrier,can achieve control of drug release in vivo,reverse the multidrug resistance of osteosarcoma cells and osteosarcoma cells to enhance the uptake of the drug can effectively inhibit tumor cell proliferation and tumor growth control,and provide carrier a new method in vivo for efficient application of chemotherapy for osteosarcoma treatment.