SCIENCE CHINA Life Sciences, Volume 61 , Issue 4 : 436-447(2018) https://doi.org/10.1007/s11427-017-9274-9

Synthesis and evaluation of a paclitaxel-binding polymeric micelle for efficient breast cancer therapy

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  • ReceivedNov 10, 2017
  • AcceptedDec 15, 2017
  • PublishedMar 19, 2018



This work was supported by the National Natural Science Foundation of China (U1501243, 51603181), the National Basic Research Program (2014CB931900), the National Natural Science Foundation of China (51603181) and the Fundamental Research Funds for the Central Universities (2016QNA4024) for financial support.

Interest statement

The author(s) declare that they have no conflict of interest.



Figure S1ƒ1H NMR spectra of PEG-G4-PEITC in DMSO-d6.

Figure S2ƒThe CMC values of polymers measured with a Nile red fluorescent method.

Figure S3ƒStability of PEG-G3-PEITC/PTX micelles.

Figure S4ƒ1H NMR spectra of PTX in CDCl3, PEG-G3-PEITC in DMSO-d6, and PEG-G3-PEITC/PTX micelles in D2O.

Figure S5ƒCytotoxicity of PEG-G3-PEITC blank micelles and PEG-PDLLA blank micelles.

Figure S6ƒChange of body weight.

Figure S7ƒHistopathologic analysis.

The supporting information is available online at http://life.scichina.com and https://link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Figure 1

    Schematic representation of self-assembly of PTX-binding polymeric micelles and the intermolecular interaction between drug and carrier. PEG-G3-PEITC/PTX micelles have improved serum stability, slowed blood clearance, and enhanced tumor accumulation.

  • Figure 2

    Characterizations of PEG-Gx-PEITC. A, 1H NMR spectrum of PEG-G3-PEITC measured in DMSO-d6. B, MALDI-TOF MS spectra. C, GPC traces (DMF, 50°C, 0.8 mL min−1).

  • Figure 3

    Characterizations of micelles. A, Sizes of PEG-G3-PEITC blank micelles, PEG-G3-PEITC/PTX, PEG-PDLLA blank micelles, and PEG-PDLLA/PTX measured by DLS in phosphate-buffered saline solution (PBS). B, TEM images of micelles. Scale bar, 200 nm.

  • Figure 4

    Study of interactions between PEG-G3-PEITC and PTX. A, 13C NMR of PTX and PTX mixed with PEG-G3-PEITC in CDCl3. The signal shift index (Δ) was defined as the chemical shift change of the carbon atom before and after mixing with carriers compared with free PTX. Sum was calculated as cumulative absolute values of the changes of all the benzene-ring carbon atoms’ chemical shifts. PTX was mixed with PEG-G3-PEITC at a molar ratio of 1:2 in accordance with the ratio in micelles. B, Fourier-transform infrared analysis (FTIR) spectra of PTX, PEG-G3-PEITC, and PEG-G3-PEITC/PTX micelles. C, X-ray diffraction (XRD) patterns of PTX, PEG-G3-PEITC, and PEG-G3-PEITC/PTX micelles.

  • Figure 5

    The drug release profiles of PEG-G3-PEITC/PTX and PEG-PDLLA/PTX micelles in mediums of PBS (0.01 mol L−1, pH 7.4 or 5.4). Data are depicted as mean±SD.

  • Figure 6

    In vitro cytotoxicity. Cytotoxicity of PEG-G3-PEITC/PTX, PEG-PDLLA/PTX micelles, and PTX against HeLa (A), MCF-7 (B), and MDA-MB-231 cells (C) after 48 h incubation. Data are depicted as mean±SD (n=6).

  • Figure 7

    Plasma pharmacokinetic profiles and biodistribution. A, Blood clearance profiles of PEG-PDLLA/PTX and PEG-G3-PEITC/PTX micelles. ICR mice (n=3) received an equivalent dose of 10 mg kg−1 PTX by intravenous injection. Blood samples were collected at 3 min and 0.5, 1, 2, 6, 12, 24 and 36 h. The concentration in the plasma was normalized as the percentage of PTX concentration at 3 min. Data are depicted as mean±SD. B, In vivo real-time biodistribution study. Nude mice bearing MCF-7 tumors received Cy5-labeled micelles (eq. 10 mg kg−1 PTX). Animals under anesthesia underwent imaging at predetermined intervals after injection (5 min and 1, 2, 5, 8, 12, 24 and 36 h). Dotted circle outlines the tumor. The urinary bladder is indicated by arrows.

  • Figure 8

    Antitumor effect. Nude mice with MCF-7 or MDA-MB-231 tumors received PBS, PEG-PDLLA/PTX, or PEG-G3-PEITC/PTX micelles (n=5, q2×5, eq. 10 mg kg−1 PTX). Dosing schedules are indicated by black arrows. A, Tumor volumes as a function of time for mice with MCF-7 tumors. B, Images of MCF-7 tumors at the end of the experiment. Dotted circle represents mice which were tumor-free. C, Tumor volumes as a function of time for mice with MDA-MB-231 tumors. D, Images of MDA-MB-231 tumors harvested at the end of the experiment. E, Histologic features of MDA-MB-231 tumors. Tissue paraffin sections were stained with hematoxylin-eosin (H&E) and examined by light microscopy. Tumor apoptosis is indicated by arrows. Data are depicted as mean±SD. Statistical significance: *, P<0.05; **, P<0.005, and ***, P<0.0005. Scale bar, 70 µm.

  • Table 1   Characterizations of polymers and PTX-loaded micelles





    Block length*







    Mn, GPC



    Mw, GPC






    CMC (mg mL−1)****




    Size of blank micelles (nm)*****




    Size of PTX-loaded micelles (nm)*****








    Zeta potential (mV)




    PTX loading content (wt.%)******




    Encapsulation efficiency (wt.%)******




    *, Determined by 1H NMR spectra. **, Determined by MALDI-TOF MS. ***, Polydispersity index (PDI) obtained by GPC. ****, Critical micelle concentration (CMC) was measured with a Nile red fluorescent method (Figure S2 in Supporting Information). *****, Measured by dynamic light scattering (DLS). ******, PTX content was determined by high-performance liquid chromatography (HPLC).

  • Table 2   of PEG-G3-PEITC/PTX, PEG-PDLLA/PTX micelles, and PTX on different cancer cell lines.


    IC50(μg PTX mL−1)
















  • Table 3   Pharmacokinetic parameters of PEG-PDLLA/PTX and PEG-G3-PEITC/PTX micelles (ICR mice, =3, intravenously, eq. PTX)





    T1/2 alpha




    T1/2 beta





    μg mL−1 h−1



    T1/2 alpha: half-life of distribution phase. T1/2 beta: half-life of elimination phases. Data are depicted as mean±SD. Statistical significance: *, P<0.05.


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