Synthesis And Application Of Acetal-responsive Polymeric Anticancer Drug Carrier

Now, cancer is a serious threat to people’s health. Methods for the treatment of cancer include radiation therapy, chemotherapy, surgical therapy and diet therapy.However, traditional methods have some shortcomings, such as traditional small molecule-antitumor drug which damage normal cell seriously and make side effects.However, intelligent macromolecular antitumor drugs enhance biological-solubility of the drug and reduced toxicity and side-effects, maintain high drug loading efficiency,prolong blood circulation time. Therefore, the intelligent macromolecular antitumor drugs show great potential in chemotherapeutic drugs.Biodegradable micelles have emerged as one of the most promising nanosystems for the controlled and targeted delivery of potent anticancer drugs. The amphiphilic block polymer are capable of self-assembly in the water, hydrophilic block spread outward and hydrophobic block contract inward, then form polymeric micelles with core-shell structure. Different pH-responsive micelles have been developed based on acid-labile bonds such as acetal, ortho ester, hydrazone, and for enhanced intracellular drug release.The thesis consists of three chapters as follows:Part I:It summarizes the current development and leading research of antitumor drug Carrier field.Part II:Synthesis, characterization of PTTMA-HPMA and PTTMA-FA-HPMA polymers,then preparation and characterization of the polymer micelles, alao antitumor drug carrier for intracellular release of DOX.Synthesis, characterization of block polymer with acetal bond by RAFT polymerization, we select HPMA(N-(2-hydroxypropyl) methacrylamide) and folic acid with passive and active targeting effect, respectively. Then preparation and characterization of the polymer micelles, such as morphology and size, CMC(critical micelle concentration) via transmission electron microscopy(TEM) and Nano size instrument, pyrene fluorescent probe technique. The in vitro acetal hydrolysis behavior and DOX release of antitumor drug carrier are studied. Base on the aboveresults, it can be concluded that HPMA-based polymer has promising potential in antitumor drug.Part III:Synthesis, characterization of PTTMA-PEG and PTTMA-FA-PEG polymers,then preparation and characterization of the polymer micelles, alao antitumor drug carrier for intracellular release of DOX.By RAFT polymerization, we synthesis, characterization of block polymer conjugates containing PEG of high biological-solubility, and functionalization of2,4,6-trimethoxybenzaldehyde and folic acid. The results show that PEG-based polymer has promising potential in antitumor drug.