Synthesis Of6-mercaptopurine HPMA Copolymer Anticancer Drugs

Cancer has become one of the major threats to human health, and showed a clearupward trend. Nowadays the main methods of treating cancer include radiationtherapy, chemotherapy, surgical therapy and gene therapy. Radiotherapy andchemotherapy are important non-surgical therapy; however, radiotherapy andchemotherapy are also serious damage to normal cells. Therefore, targetedcopolymers for environment-triggered intracellular anticancer drug release havebecome the focus of today’s research.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. HPMA copolymers accumulate selectively in tumor sites because of theenhanced permeation and retention (EPR) effect, thus overcoming limitations of drugrelated toxicities.6-Mercaptopurine (6-MP) has been considered as one of the most efective drugsused in cancer chemotherapy，it is used to treat leukemia and other similar neoplastic.The effect of6-MP on tumour cells has been investigated that the activity of6-MP isdue to its conversion into the corresponding ribosides by the tumour cells.This paper was consisted by two parts as follow:PartⅠ:Summarize the development history of anti-cancer drugs containing disulfidebond.PartⅡ:N-(2-hydroxypropyl) methacrylamide (HPMA) is selected as drug carrier.P(HPMA)-P(6-Mercaptopurine) containing disulfide bond for redox-triggeredintracellular anticancer drug release was synthesized via radical precipitationpolymerization. The copolymer was characterized by1HNMR. The results showed that6-Mercaptopurine could be released from P(HPMA)-P(6-Mercaptopurine) in thepresence of DTT.Part III:Galactose was selected as active targeted ligand.P(HPMA)-P(Galactose)-P(6-Mercaptopurine) containing galactose for activetargeting and disulfide bond for redox-triggered intracellular anticancer drug releasewas synthesized and characterized.