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Acta Phys. -Chim. Sin.  2016, Vol. 32 Issue (10): 2628-2635    DOI: 10.3866/PKU.WHXB201606296
ARTICLE     
Preparation of Fluorescently Labeled pH-Sensitive Micelles for Controlled Drug Release
Wei-Ju HAO1,Jun-Qi ZHANG2,Ya-Zhuo SHANG1,Shou-Hong XU1,*(),Hong-Lai LIU1
1 State Key Laboratory of Chemical Engineering, Department of Chemistry, East China University of Science and Technology, Shanghai 200237, P. R. China
2 Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P. R. China
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Abstract  

In this paper, novel pH-sensitive amphiphilic diblock copolymers[mPEG-b-PDPAn (n=100-200, polymerization degree; PEG is polyethylene glycol and PDPA is polydiphenylamine)] with and without a fluorescent group (fluorescein isothiocyanate, FITC) were synthesized by atom transfer radical polymerization (ATRP). The copolymers were used to prepare micelles by solvent evaporation to act as drug carriers. The micelles were spherical with a uniform diameter of 180-240 nm (0.3 mg·mL-1). The model drug doxorubicin (DOX) could be encapsulated into the micelles with a high loading efficiencyof about 11% (w, mass fraction). The micelles were stable at pH 7.4 and became looser upon the protonation of the PDPA block in a weakly acidic environment. The release of DOX accelerated when the micelles were exposed to weakly acidic conditions, and the amount released reached 80%after 2-3 h. Cell toxicity assays of the micelles were carried out using human cancer cells (Huh7), and the micelles showed good cytocompatibility. The micelles labeled with FITC displayed high cell transfection efficiency. As a result, micelles labeled with fluorescent groups may open up new perspectives for real-time tracking of drug delivery and/or distribution during chemotherapy.



Key wordspH-sensitive copolymer      Self-assembly micelle      Targeting delivery      Controlled release     
Received: 25 April 2016      Published: 29 June 2016
MSC2000:  O648  
Fund:  the National Natural Science Foundation of China(21276074);Fundamental Research Funds for the Centre Universities of China(?)
Corresponding Authors: Shou-Hong XU     E-mail: xushouhong@ecust.edu.cn
Cite this article:

Wei-Ju HAO,Jun-Qi ZHANG,Ya-Zhuo SHANG,Shou-Hong XU,Hong-Lai LIU. Preparation of Fluorescently Labeled pH-Sensitive Micelles for Controlled Drug Release. Acta Phys. -Chim. Sin., 2016, 32(10): 2628-2635.

URL:

http://www.whxb.pku.edu.cn/10.3866/PKU.WHXB201606296     OR     http://www.whxb.pku.edu.cn/Y2016/V32/I10/2628

Fig 1  (a) 1H nuclear magnetic resonance (1H NMR) spectra of the polymers (1) PEG-Br,(2) PEG-PDPA,(3) FITC-PEG-Br,and (4) FITC-PEG-PDPA; (b) the gel permeation chromatography (GPC) data of polymers; (c) size changes of the block polymers at different pH values mPEG: methoxypolyethylene glycols; PDPA: poly[2-(diisopropylamino) ethylmethacrylate]; FITC: fluorescein isothiocyanate; Mn: number-average molecular weight; m: mass
Polymerc/(mg?mL-1)Size/nmPDI105 CMC/(mmol?L-1)Zeta potential/mV
mPEG45-PDPA1000.1203.3 ± 15.30.114 ± 0.00530.9-12.35 ± 1.55
0.3240.1 ± 15.30.148 ± 0.005-10.31 ± 1.55
0.5306.3 ± 15.30.279 ± 0.005-9.41 ± 1.55
FITC-PEG45-PDPA1000.3215.3 ± 15.30.096 ± 0.005-10.71 ± 1.55
mPEG45-PDPA1500.1193.7 ± 15.30.144 ± 0.0057.94-3.45 ± 1.55
0.3232.3 ± 15.30.151 ± 0.005-2.75 ± 1.55
0.5272.4 ± 15.30.166 ± 0.005-2.34 ± 1.55
mPEG45-PDPA2000.1168.3 ± 15.30.077 ± 0.0053.09-3.16 ± 1.55
0.3186.3 ± 15.30.081 ± 0.005-2.56 ± 1.55
0.5265.5 ± 15.30.059 ± 0.005-0.05 ± 1.55
Table 1  Properties of micelles composed of copolymers by self-assembly (pH 7.4)
Fig 2  (a) TEM images of polymer micelles; (b) particle sizes of micelles (a) pH7.4, the concentration was 0.3 mg?mL-1.
Fig 3  Drug release dynamic of micelles at different pH values
Fig 4  1H NMR spectral evolution with time of the micelles composed of mPEG45-PDPA10 under acidic condition (0.3 mg?mL-1)
Fig 5  Cell viability of Huh7 cells cultured with different concentrations (c) of micelles
Fig 6  Transfection of the micelles composed of polymers mPEG45-PDPA100 and FITC-PEG45-PDPA100 (mole ratio,1 : 1)
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