The targeting behavior of folate-nanohydrogel evaluated by near infrared imaging system in tumor-bearing mouse model.
OBJECTIVE
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.


METHODS
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.


RESULTS
Spherical folate-NHG with diameter of about 50 nm and LCST of about 40 degrees 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.


CONCLUSIONS
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.
Zhang
Jian
J
Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Tongjia Lane No. 24, Nanjing, 210009, People's Republic of China.
Deng
Dawei
D
Qian
Zhiyu
Z
Liu
Fei
F
Chen
Xinyang
X
An
Lianxiao
L
Gu
Yueqing
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy; D010316:Particle Size; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D020100:Hydrogels; D005492:Folic Acid