Skip to main content Accessibility help

Design, synthesis, and characterization of glycyrrhetinic acid-mediated multifunctional liver-targeting polymeric carrier materials

  • Qingxia Guan (a1), Xue Zhang (a1), Yue Zhang (a1), Xin Yu (a1), Weibing Zhang (a1), Liping Wang (a1), Shuang Sun (a1), Xiuyan Li (a1), Yanhong Wang (a1), Shaowa Lv (a1) and Yongji Li (a1)...


The purpose of this study was to construct a glycyrrhetinic acid (GA)-mediated, breakable, intracellular, nanoscale drug-delivery carrier via amide and esterification reactions. The structures were identified by Fourier-transformed infrared (FTIR) and 1H-nuclear magnetic resonance (1H-NMR) spectrophotometry. The compatibility and safety of the carrier were evaluated using hemolysis and cytotoxicity tests. The GA-copolymer micelle was prepared using the solvent evaporation method. FTIR and 1H-NMR detection demonstrated the successful construction of the polymer. No hemolysis occurred in any concentration of polymer within 3 h, and the hemolysis rate was less than 5%. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) experimental results showed that the novel polymer reduced the cell survival rate and had significant cytotoxic effects. The blank nanoparticles were liquid with light blue opalescence. Transmission electron microscopy revealed that the empty micelles were uniform spheres, with an average size of 62 nm and a zeta potential of −13 mV. The novel GA-mediated polymeric carrier material developed here has the potential to effectively kill human SMMC-7721 cancer cells within 3 days when the dose is above 500 ug/mL.


Corresponding author

a)Address all correspondence to these authors. e-mail:


Hide All
1.Gao, Y., Li, W., Liu, R., Guo, Q., Li, J., Bao, Y., Zheng, H., Jiang, S., and Hua, B.: Norcantharidin inhibits IL-6-induced epithelial-mesenchymal transition via the JAK2/STAT3/TWIST signaling pathway in hepatocellular carcinoma cells. Oncol. Rep. 38, 1224 (2015).
2.Shen, L., Zhang, G., Lou, Z., Xu, G., and Zhang, G.: Cryptotanshinone enhances the effect of Arsenic trioxide in treating liver cancer cell by inducing apoptosis through downregulating phosphorylated-STAT3 in vitro and in vivo. BMC Complementary Altern. Med. 17, 106 (2017).
3.Johnson, P.J.: Hepatocellular carcinoma: Is current therapy really altering outcome? Gut 51, 459 (2002).
4.Palmer, D.H., Hussain, S.A., and Johnson, P.J.: Systemic therapies for hepatocellular carcinoma. Expert Opin. Invest. Drugs 13, 1555 (2004).
5.Mukherjee, A., Kumar, B., Hatano, K., Russell, L., Trock, B., Searson, P., Meeker, A., Pomper, M., and Lopold, S.: Development and application of a novel model system to study ‘active’ and ‘passive’ tumor targeting. Mol. Cancer Ther. 15, 2541 (2016).
6.Thepphankulngarm, N., Wonganan, P., Sapcharoenkun, C., Tuntulani, T., and Leeladee, P.: Combining vitamin B12 and cisplatin-loaded porous silica nanoparticles via coordination: A facile approach to prepare a targeted drug delivery system. New J. Chem. 41, 13823 (2017).
7.Paschkunova-Martic, I., Kremser, C., Mistlberger, K., Shcherbakova, N., Dietrich, H., Talasz, H., Zou, Y., Hugl, B., Galanski, M., Sölder, E., Pfaller, K., Höliner, I., Buchberger, W., Keppler, B., and Debbage, P.: Design, synthesis, physical and chemical characterisation, and biological interactions of lectin-targeted latex nanoparticles bearing Gd-DTPA chelates: An exploration of magnetic resonance molecular imaging (MRMI). Histochem. Cell Biol. 123, 283 (2005).
8.Songfeng, E., Lei, S., and Guo, Z.: Magnetic and pH sensitive drug delivery system through NCA chemistry for tumor targeting. RSC Adv. 4, 15856 (2014).
9.Jiang, W., Wu, J., Shen, Y., Tian, R., Zhou, S., and Jiang, W.: Synthesis and characterization of doxorubicin loaded pH-sensitive magnetic core–shell nanocomposites for targeted drug delivery applications. Nano 11, 1650127 (2016).
10.Hillery, A.: Heat-sensitive liposomes for tumour targeting. Drug Discov. Today 6, 224 (2001).
11.Babincová, M., Babinec, P., and Bergemann, C.: High-gradient magnetic capture of ferrofluids: Implications for drug targeting and tumor embolization. Z. Naturforsch. C Biosci. 56, 909 (2001).
12.Yang, Y.F., Xie, X.Y., Yang, Y., Zhang, H., and Mei, X.G.: A review on the influences of size and surface charge of liposome on its targeted drug delivery in vivo. Acta Pharm. Sin. 48, 1644 (2013).
13.Mori, Y., Umeda, M., Fukunaga, M., Ogasawara, K., and Yoshioka, Y.: MR contrast in mouse lymph nodes with subcutaneous administration of iron oxide particles: Size dependency. Magn. Reson. Med. Sci. 10, 219 (2011).
14.Yan, J.J., Liao, J.Z., Lin, J.S., and He, X.X.: Active radar guides missile to its target: Receptor-based targeted treatment of hepatocellular carcinoma by nanoparticulate systems. Tumor Biol. 36, 55 (2015).
15.Maeda, H., Fang, J., Ulbrich, K., Tomas, E., and Nekamura, H.: Missile-type tumor-targeting polymer drug, P-THP, seeks tumors via three different steps based on the EPR effect. Gan to Kagaku Ryoho 43, 549 (2016).
16.Di, L., Feng, X., Chen, L., Ding, J., and Chen, X.: One-step synthesis of targeted acid-I abile polysaccharide prodrug for efficiently intracellular drug delivery. ACS Biomater. Sci. Eng. 4, 539 (2017).
17.Torchilin, V.P.: Micellar nanocarriers: Pharmaceutical perspectives. Pharm. Res. 24, 1 (2007).
18.Yang, L.: Gene Transporters Based on Stimulus-Responsive Polymers (University of Science and Technology of China, Hefei, Anhui, China, 2017); p. 1.
19.Kataoka, K., Harada, A., and Nagasaki, Y.: Block copolymer micelles for drug delivery: Design, characterization and biological significance. Adv. Drug Deliv. Rev. 64, 37 (2012).
20.Gaucher, G., Dufresne, M.H., Sant, V.P., Kang, N., Maysinger, D., and Leroux, J.C.: Block copolymer micelles: Preparation, characterization, and application in drug delivery. J. Controlled Release 109, 169 (2005).
21.Torchilin, V.: Tumor delivery of macromolecular drugs based on the EPR effect. Adv. Drug Deliv. Rev. 63, 131 (2011).
22.Hou, L., Yao, J., Zhou, J.P., and Zhang, Q.: Pharmacokinetics of a paclitaxel-loaded low molecular weight heparin-all-trans retinoid acid conjugate ternary nanoparticulate drug delivery system. Biomaterials 33, 5431 (2012).
23.Wang, J., Yin, C., Tang, G., Lin, X., and Wu, Q.: Glucose-functionalized multidrug-conjugating nanoparticles based on amphiphilic terpolymer with enhanced anti -tumorous cell cytotoxicity. Int. J. Pharm. 441, 291 (2013).
24.Liang, D.S., Su, H.T., Liu, Y.J., Wang, A.T., and Qi, X.R.: Tumor-specific penetrating peptides-functionalized hyaluronic acid-D-α-tocopheryl succinate based nanoparticles for multi-task delivery to invasive cancers. Biomaterials 71, 11 (2015).
25.Zou, D., Wang, W., Lei, D.X., Yin, Y., Ren, P., Chen, J.J., Yin, T.Y., Wang, B.C., Wang, G.X., and Wang, Y.Z.: Penetration of blood–brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system. Int. J. Nanomed. 12, 4879 (2017).
26.Wejdan, A.S., Ali, A., Curtis, A.D.M., and Hoskins, C.: Dual acting polymeric nano-aggregates for liver cancer therapy. Pharmaceutics 10, 63 (2018).
27.Min, L., Wei, Y.Z., Bi, R.W., Yang, G., Zi, F.S., and Chang, Z.Q.: Ligand-based targeted therapy: A novel strategy for hepatocellular carcinoma. Int. J. Nanomed. 11, 5645 (2016).


Type Description Title
Supplementary materials

Guan et al. supplementary material
Guan et al. supplementary material

 Unknown (116 KB)
116 KB

Design, synthesis, and characterization of glycyrrhetinic acid-mediated multifunctional liver-targeting polymeric carrier materials

  • Qingxia Guan (a1), Xue Zhang (a1), Yue Zhang (a1), Xin Yu (a1), Weibing Zhang (a1), Liping Wang (a1), Shuang Sun (a1), Xiuyan Li (a1), Yanhong Wang (a1), Shaowa Lv (a1) and Yongji Li (a1)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.