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

DOI: 10.1007/s11095-009-0005-1

Cite this article as:
Zhang, J., Deng, D., Qian, Z. et al. Pharm Res (2010) 27: 46. doi:10.1007/s11095-009-0005-1

Abstract

Purpose

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°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.

KEY WORDS

active targetingfolate receptornanohydrogelNIR imagingtumor

Abbreviations

AAm

Acrylamide

AAn

Allylamine

BIS

N,N-methylene-bis-acrylamide

CCD

charge-coupled device

CT

computed tomography

DCC

N, N’-Dicyclohexylcarbodiimide

DCU

dicyclohexylurea

D-folate-NHG

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

DMSO

dimethyl sulfoxide

FBP

folate binding protein

FoAAn

folate-Allylamine

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

P[(Folate-Allylamine)-co-(N-isopropylacrylamide)-co-Acrylamide]

FR

folate receptor

KPS

Potassium persulfate

LC

loading content

LC-MS

liquid chromatograph-mass spectrum

LCST

lower critical solution temperature

LPSA

laser particle size analyzer

MR

magnetic resonance

MTT

methyl thiazolyl tetrazolium

NHG

nanohydrogel

NHS

N-hydroxysuccinimide

NIPA

N-isopropylacryl-amide

NIR

near infrared

NIRD-12

No.12 near infrared dye

non-NHG

P[(N-isopropylacrylamide)-co-Acrylamide]

PNIPA

P(N-isopropylacrylamide)

ROI

region of interest

RPMI

Roswell Park Memorial Institute

RT

room temperature

SBF

simulated body fluid

SDS

sodiumdodecyl sulfate

TEA

triethanolamine

TEM

transmission electron microscope

US

ultrasonography

Wt%

((WAAm/WNIPA) × 100%)

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