Synthesis Of Poly (HPMA)-(HNA) Anti-Cancer Drug And Branched Polyethylene Carriers

Cancer is a leading cause of death around the world. The World HealthOrganization estimates that84million people will die of cancer between2005and2015. Especially, Hepatocellular carcinoma (HCC) is the fifth most frequentlydiagnosed cancer worldwide. Conventional chemotherapy drugs can suppress tumoursby restraining tumour vessel growth and preventing the repair of damaged vascularendothelial cells, however they can not identified specifcally normal and tumoralcells. The ultimate goal of cancer therapeutics is to increase the survival time and thequality of life of the patient by reducing the systemic toxicity of chemotherapy. Foreffective cancer therapy, it is necessary to discover new anti-cancer drugs and developnovel biomedical technologies.With the development of drug studies, biological materials science and clinicalmedicine, polymer materials began to act as a drug carrier in the chemical field ofmedicine. N-(2-hydroxypropyl methacrylamide (HPMA) copolymers arebiocompatible, nonimmunogenic, and nontoxic, and their body distribution is wellcharacterized. HPMAcopolymers accumulate selectively in tumor sites because of theenhanced permeation and retention (EPR) effect, thus overcoming limitations of drugrelated toxicities.2-hydroxy-1,4-naphthoquinone is one of the naphthoquinone compounds.Some of these compounds have been reported to exhibit a variety of biologicalactivities. Kamei had studied the inhibit cell growth test with the quinone compounds,he found the quinone compounds mainly inhibite the S phase of the cell growth, thecytotoxic was depended on the number of phenolic hydroxyl groups from thecompounds.This paper was consisted by two parts as follow:PartⅠ:The HPMA was choosed as the drug carrier, the novel2-hydroxy-1,4-naphthoquinone HPMA copolymer conjugates was synthesized and characterizated.We found this type of polymer drugs have good anti-tumor activity by experimental invitro and in vivo. PartⅡIn recent years, with the development of late transition metal catalysts for olefinpolymerization,“Chain Walking Polymerization CWP” catalyzed by Ni(Ⅱ)/Pd(Ⅱ)-α-diimine complexes has attracted more and more attentions due to its ability toproduce hyperbranched and dendritic polymer under low ethylene pressure. Chainwalking polymerization (CWP) followed by atom transfer radical polymerization(ATRP), can synthesize water-soluble core-shell [core: polyethylene, PE; shell:oligo(ethylene glycol), OEG] dendritic nanoparticles with tunable sizes and reactivesurface functionalities efficiently. The nanosized dendrimers have shown greatpotential in the anticancer drug delivery systems. In this work, several α-diimineNi(Ⅱ) complexes was synthesied and characterizated and been used in thepolymerization of ethylene. We chose one of the complexes to the polymerization ofStyrene and the copolymerization of ethey and MMA. The influence of different stericeffects and electron densities of the metal center on the catalyst activity, in particular,on the microstructure and size of the polymer was studied, it will laid the foundationfor futher synthesies nano-dendrimers to anticancer drug delivery systems withtransition metal diimine catalysts.