title: Dextran-b-poly(L-histidine) copolymer nanoparticles for ph-responsive drug delivery to tumor cells.
abstract: OBJECTIVE
  Nanoparticles based on stimuli-sensitive drug delivery have been extensively investigated for tumor targeting. Among them, pH-responsive drug targeting using pH-sensitive polymers has attracted attention because solid tumors have an acidic environment. A dextran-b-poly(L-histidine) (DexPHS) copolymer was synthesized and pH-responsive nanoparticles were fabricated for drug targeting.
  
  
  RESULTS
  A DexPHS block copolymer was synthesized by attaching the reductive end of dextran to the amine groups of poly(L-histidine). pH-responsive nanoparticles incorporating doxorubicin were fabricated and studied in HuCC-T1 cholangiocarcinoma cells. Synthesis of DexPHS was confirmed by 1H nuclear magnetic resonance spectroscopy, with specific peaks of dextran and PHS observed at 2-5 ppm and 7.4-9.0 ppm, respectively. DexPHS nanoparticles showed changes in particle size with pH sensitivity, ie, the size of the nanoparticles increased at an acidic pH and decreased at a basic pH. DexPHS block copolymer nanoparticles incorporating doxorubicin were prepared using the nanoprecipitation dialysis method. The doxorubicin release rate was increased at acidic pH compared with basic pH, indicating that DexPHS nanoparticles have pH-sensitive properties and that drug release can be controlled by variations in pH. The antitumor activity of DexPHS nanoparticles incorporating doxorubicin were studied using HuCC-T1 cholangiocarcinoma cells. Viability was decreased in cells treated with nanoparticles at acidic pH, whereas cell viability in response to treatment with doxorubicin did not vary according to changes of pH.
  
  
  CONCLUSIONS
  Our results indicated that DexPHS polymeric micelles are promising candidates for antitumor drug targeting.
authors.affiliation: Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Hwang
authors.forename: Cheol Woong
authors.initials: CW
authors.lastname: Choi
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Kim
authors.forename: Do Hyung
authors.initials: DH
authors.lastname: Kim
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kwak
authors.forename: Hye Myeong
authors.initials: HM
authors.lastname: Lee
authors.forename: Cy Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Chung Wook
authors.initials: CW
authors.lastname: Chung
authors.forename: Young-Ii
authors.initials: YI
authors.lastname: Jeong
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D011108:Polymers / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D004337:Drug Carriers; D011108:Polymers; C033223:polyhistidine; D006639:Histidine; D004317:Doxorubicin
keywords: block copolymer; dextran; nanoparticles; pH-responsive drug targeting; poly(L-histidine)