The Preparation Of Multifunctional Anti Cancer Prodrug Based On Aliphatic Polyester

In recent years,malignant tumors spread throughout the world and the prevalence of this disease extends from the developed countries to developing countries.Because of its low cure,rapid onset and high treatment costs,leads to "peoples afraid of talking about cancer".Through the efforts and exploration of medical professionals from all over the world,the methods of surgical treatment,laser therapy,magnetic therapy and chemotherapy have been developed and optimized.Among them,chemotherapy has attracted extensive attention as a simple,effective,and low risky treatment method,which has been developed and optimized continuously.Aliphatic polyester is a kind of hydrophobic biodegradable material and biological medicine commonly used with PCL,PLA and PLGA.They are used as drug carrier and hydrophilic substances together to build a water soluble amphiphilic substance or two.In this thesis,we have synthesized two different two drug delivery systems for the preparation of two different antitumor drug delivery systems.Studies have shown that hydrophilic polymers are not conducive to phagocytosis by cells and a large number of nanoparticles are released before the tumor is swallowed by the cells,so the rate of drug absorption is low.In this paper,we design a hydrophilic shell nano intelligent response to tumor sites in nano drug by local injection of glutathione(GSH)makes the hydrophilic nano drug end off,so as to improve the rate of drug absorption.In this paper we use the response to a group of chain segments of hydrophilic segment bonded to the hydrophobic block polymer and another segment on the bonding of antitumor drugs,getting a reduction responsive antitumor prodrugs.By 1H NMR,GPC and HPLC characterization,it showed that the prodrug was successfully prepared.In vitro experiments,it also showed that the drug delivery system can be prepared in a tumor cell to destroy and release drugs to kill tumor cells,without killing the normal tissue cells.Therefore,the reduced response prodrug prepared in this topic met the requirements of this design.It is also based on the diagnosis and treatment of tumors with a nano system of polycaprolactone polylactide and preparation.Medicine for cancer treatment also needs the condition monitoring(i.e.diagnosis).Diagnosis and treatment of the traditional medical mode are carried out separately and a course takes a long time,which will increase the economic and body burden of the patients.If the function of diagnosis and treatment can be set in alone system,it will solve the above problems.Therefore,some researchers are developing a set of treatment and diagnosis in one system and have made a series of progress.The commonly used diagnostic reagents are organic fluorescent probes,gold nanoparticles and quantum dots.In this paper,we firstly use polyethylene glycol monomethyl ether functionalized caprolactone initiated in monomer and lactide monomers to get a amphiphilic triblock copolymer,then through the "thiol-bromide" and "thiol-bromo" click reaction on the polymer bonding of paclitaxel and lipoic acid,finally encapsulated quantum reaction get a nano theranostic system by ligand exchange.The characterization of DLS and TEM showed that the size of nanoparticles was within the range of cell endocytosis and the distribution was narrow.The results of in vitro cell experiments showed that the system have a good effect in killing tumor cells.The endocytosis experiments with CLSM showed that the system had a strong quantum dot fluorescence.Therefore,we can conclude that this nanotheranostic based on quantum dots and polymer prodrugs has been successfully prepared.