Pharmaceutical Research

, 27:46

The Targeting Behavior of Folate-Nanohydrogel Evaluated by Near Infrared Imaging System in Tumor-Bearing Mouse Model

  • Jian Zhang
  • Dawei Deng
  • Zhiyu Qian
  • Fei Liu
  • Xinyang Chen
  • Lianxiao An
  • Yueqing Gu
Research Paper



To synthesize P[(Folate-Allylamine)-co-(N-isopropylacrylamine)- co-Acrylamide] (P(FoAAn-co-NIPA-AAm), folate-NHG) with appropriate diameter and lower critical solution temperature (LCST) for targeting to folate receptor (FR) expressing tumors.


Folate-NHG was synthesized by free-radical precipitation polymerization method reported in our previous work and other reports. LCST, diameter and morphology of folate-NHG were characterized by UV-vis spectrophotometer, laser particle size analyzer (LPSA) and transmission electron microscope (TEM), respectively. No.12 near infrared dye (NIRD-12) was entrapped into folate-NHG by hydrophobic association to trace the in vivo dynamic behavior of folate-NHG. This process was evaluated by a homemade near infrared (NIR) imaging system.


Spherical folate-NHG with diameter of about 50 nm and LCST of about 40°C was successfully synthesized. The photo stability of NIRD-12 was strengthened after being entrapped into folate-NHG, which enabled NIRD-12 to better trace the in vivo dynamic process of folate-NHG. Folate-NHG showed good targeting capability for all three folate receptor expressing tumor models (SMMC-7721, Bel-7402 and HeLa) with different sizes, and this accumulation could last for more than 96 h. D-folate-NHG, synthesized with double amount of FoAAn, showed better targeting effect for SMMC-7721 tumor model than that of folate-NHG.


Folate-NHG could actively accumulate in three models of folate receptor positive tumors with different sizes and keep retention for more than 96 h, which enables it to be used as a diagnostic reagent or anti-tumor drug carrier for tumor therapy.


active targeting folate receptor nanohydrogel NIR imaging tumor 









charge-coupled device


computed tomography


N, N’-Dicyclohexylcarbodiimide




special folate-NHG synthesized with as double amount of FoAAn as that of folate-NHG


dimethyl sulfoxide


folate binding protein



folate-NHG or P(FoAAn-co-NIPA-co-AAm)



folate receptor


Potassium persulfate


loading content


liquid chromatograph-mass spectrum


lower critical solution temperature


laser particle size analyzer


magnetic resonance


methyl thiazolyl tetrazolium








near infrared


No.12 near infrared dye






region of interest


Roswell Park Memorial Institute


room temperature


simulated body fluid


sodiumdodecyl sulfate




transmission electron microscope




((WAAm/WNIPA) × 100%)


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jian Zhang
    • 1
  • Dawei Deng
    • 1
  • Zhiyu Qian
    • 2
  • Fei Liu
    • 1
  • Xinyang Chen
    • 1
  • Lianxiao An
    • 1
  • Yueqing Gu
    • 1
  1. 1.Department of Biomedical Engineering, School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  2. 2.Department of Biomedical Engineering, School of AutomationNanjing University of Aeronautics and AstronauticssNanjingPeople’s Republic of China

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