Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-22T20:06:05.779Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  26 May 2020

Qingxia Guan ,
Xue Zhang ,
Yue Zhang ,
Xin Yu ,
Weibing Zhang ,
Liping Wang ,
Shuang Sun ,
Xiuyan Li ,
Yanhong Wang  and
Shaowa Lv
...Show all authors
Qingxia Guan
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Xue Zhang
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Yue Zhang
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Xin Yu
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Weibing Zhang
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Liping Wang
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Shuang Sun
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Xiuyan Li
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Yanhong Wang
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Shaowa Lv*
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
Yongji Li*
Affiliation:
College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang 150040, China
*
a)Address all correspondence to these authors. e-mail: [email protected]
b)e-mail: [email protected]
Get access

Abstract

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.

Keywords

hepatocellular carcinomaglycyrrhetinic acidpolymeric carrier materialself-assemblymicelles
Type
Article
Information
Journal of Materials Research , Volume 35 , Issue 10 , 28 May 2020 , pp. 1236 - 1248
Copyright
Copyright © Materials Research Society 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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).CrossRefGoogle Scholar
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).CrossRefGoogle ScholarPubMed
Johnson, P.J.: Hepatocellular carcinoma: Is current therapy really altering outcome? Gut 51, 459 (2002).CrossRefGoogle ScholarPubMed
Palmer, D.H., Hussain, S.A., and Johnson, P.J.: Systemic therapies for hepatocellular carcinoma. Expert Opin. Invest. Drugs 13, 1555 (2004).CrossRefGoogle ScholarPubMed
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).CrossRefGoogle ScholarPubMed
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).CrossRefGoogle Scholar
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).CrossRefGoogle Scholar
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).Google Scholar
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).CrossRefGoogle Scholar
Hillery, A.: Heat-sensitive liposomes for tumour targeting. Drug Discov. Today 6, 224 (2001).CrossRefGoogle ScholarPubMed
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).CrossRefGoogle ScholarPubMed
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).Google ScholarPubMed
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).CrossRefGoogle ScholarPubMed
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).CrossRefGoogle ScholarPubMed
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).Google ScholarPubMed
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).Google Scholar
Torchilin, V.P.: Micellar nanocarriers: Pharmaceutical perspectives. Pharm. Res. 24, 1 (2007).CrossRefGoogle ScholarPubMed
Yang, L.: Gene Transporters Based on Stimulus-Responsive Polymers (University of Science and Technology of China, Hefei, Anhui, China, 2017); p. 1.Google Scholar
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).CrossRefGoogle Scholar
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).CrossRefGoogle ScholarPubMed
Torchilin, V.: Tumor delivery of macromolecular drugs based on the EPR effect. Adv. Drug Deliv. Rev. 63, 131 (2011).CrossRefGoogle ScholarPubMed
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).CrossRefGoogle ScholarPubMed
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).CrossRefGoogle ScholarPubMed
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).CrossRefGoogle ScholarPubMed
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).Google ScholarPubMed
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).Google Scholar
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).Google Scholar
Supplementary material: Image

Guan et al. supplementary material

Guan et al. supplementary material

Download Guan et al. supplementary material(Image)
Image 116 KB