title: Folic-acid-conjugated pullulan/poly(DL-lactide-co-glycolide) graft copolymer nanoparticles for folate-receptor-mediated drug delivery.
abstract: BACKGROUND
  Nanoparticles have been extensively investigated for targeted delivery of anticancer drugs. Since the folate receptor is universally over-expressed on the tumor cell membrane, folic acid is often used to modify the fate of nanoparticles in biologicals.
  
  
  METHODS
  To fabricate targetable nanoparticles, folic acid was conjugated to a pullulan backbone and poly(DL-lactide-co-glycolide) (PLGA) (abbreviated as FAPuLG) was conjugated. KB cells and NIH3T3-cell-bearing mice were prepared to prove folate receptor targeting of FAPuLG nanoparticles.
  
  
  CONCLUSIONS
  Nanoparticles of FAPuLG copolymer that self-assembled in water were small with diameters <200 nm. Doxorubicin (DOX) as a model drug was incorporated into the FAPuLG nanoparticles that were used to treat folate receptor over-expressing KB human carcinoma cells. Fluorescence microscopy revealed that DOX-incorporated FAPuLG nanoparticles induced strong red fluorescence in the KB cells in the absence of folic acid. However, fluorescence intensity was decreased by blocking folate receptors. Antitumor activity of FAPuLG nanoparticles against KB cells in vitro was also decreased by blocking folate receptors. In animal study using near-infrared dye-conjugated FAPuLG nanoparticles, fluorescence intensity was significantly higher at KB solid tumor than that of NIH3T3.
  
  
  CONCLUSIONS
  The results indicate that FAPuLG nanoparticles can target the folate receptor of tumor cells. FAPuLG nanoparticles are a promising candidate for active targeting of anticancer agents.
authors: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 501-746 Korea.
authors: Sang Joon
authors: SJ
authors: Lee
authors: Biomedical Research Institute, Pusan National University Hospital, Pusan, 602-739 Republic of Korea.
authors: Yong-Ho
authors: YH
authors: Shim
authors: Department of Microbiology, Chonnam National University Medical School, Gwangju, 501-746 Korea.
authors: Jong-Suk
authors: JS
authors: Oh
authors: Department of Microbiology, Chonnam National University Medical School, Gwangju, 501-746 Korea.
authors: Young-Il
authors: YI
authors: Jeong
authors: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 501-746 Korea.
authors: In-Kyu
authors: IK
authors: Park
authors: Department of Microbiology, Chonnam National University Medical School, Gwangju, 501-746 Korea.
authors: Hyun Chul
authors: HC
authors: Lee
keywords: Drug targeting; Folate receptor; KB cells; Nanoparticles; Pullulan