Biomedical Microdevices

, 21:18 | Cite as

Targeted delivery of 20(S)-ginsenoside Rg3-based polypeptide nanoparticles to treat colon cancer

  • Renna Qiu
  • Feng Qian
  • Xiaofeng Wang
  • Hongjun LiEmail author
  • Lizhe WangEmail author


Colorectal cancer (CRC) is a major malignancy characterized by a high metastasis rate. Systematic chemotherapy is important for patients with advanced CRC. However, many limitations (e.g., side effects to normal organs, shorter circulation time, and unsatisfactory tumor inhibition results) of traditional chemotherapy restrict its further application. Thus, it is necessary to find a method to overcome these challenges and improve the efficacy of CRC treatment. In this study, 20(S)-ginsenoside (Rg3) co-loaded poly(ethylene glycol)-block-poly(L-glutamic acid-co-L-phenylalanine) (mPEG-b-P(Glu-co-Phe)) nanoparticles (Rg3-NPs) were prepared. mPEG-b-P(Glu-co-Phe)-based drug delivery systems are pH sensitive that can target cancer cells and circulate for longer in blood. Rg3 could be released rapidly from the nanoparticles within tumor cells. A subcutaneous colon cancer mouse model was developed to evaluate the anticancer efficiency of the Rg3-NPs. The in vivo study indicated that the Rg3-NPs could significantly inhibit tumor proliferation by decreasing the expressions of proliferating cell nuclear antigen, resulting in tumor apoptosis through the increased expressions of caspase-3. Our study demonstrated the marked potential of the Rg3-NPs to treat CRC.


Colorectal cancer CRC Chemotherapy 20(S)-ginsenoside Rg3 Nanoparticles 



This work was supported by Talents Team Major Program of Jilin Province of China (JRCBTZ. [2016] No. 3).

Compliance with ethical standards

Conflict of interest

The authors report no declarations of interest.


  1. M. Abbas, Q.L. Zou, S.K. Li, X.H. Yan, Self-assembled peptide- and protein-based nanomaterials for antitumor photodynamic and Photothermal therapy. Adv. Mater. 29(12) (2017)CrossRefGoogle Scholar
  2. A.S. Attele, J.A. Wu, C.S. Yuan, Ginseng pharmacology - multiple constituents and multiple actions. Biochem. Pharmacol. 58(11), 1685–1693 (1999)CrossRefGoogle Scholar
  3. J. Cheng, J.-X. Ding, Y.-C. Wang, J. Wang, Synthesis and characterization of star-shaped block copolymer of poly(epsilon-caprolactone) and poly(ethyl ethylene phosphate) as drug carrier. Polymer 49(22), 4784–4790 (2008)CrossRefGoogle Scholar
  4. H.M.C. Cheung, P.J. Karanicolas, E. Hsieh, N. Coburn, T. Maraj, J.K. Kim, et al., Late gadolinium enhancement of colorectal liver metastases post-chemotherapy is associated with tumour fibrosis and overall survival post-hepatectomy. Eur. Radiol. 28(8), 3505–3512 (2018)CrossRefGoogle Scholar
  5. K. Cho, X. Wang, S. Nie, Z. Chen, D.M. Shin, Therapeutic nanoparticles for drug delivery in cancer. Clin. Cancer Res. 14(5), 1310–1316 (2008)CrossRefGoogle Scholar
  6. M.A. Cobleigh, C.L. Vogel, D. Tripathy, N.J. Robert, S. Scholl, L. Fehrenbacher, et al., Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J. Clin. Oncol. 17(9), 2639–2648 (1999)CrossRefGoogle Scholar
  7. J.A.A. DeLuca, E.L. Garcia-Villatoro, C.D. Allred, Flaxseed bioactive compounds and colorectal Cancer prevention. Curr. Oncol. Rep. 20(8), 59 (2018)CrossRefGoogle Scholar
  8. J. Essers, A.F. Theil, C. Baldeyron, W.A. van Cappellen, A.B. Houtsmuller, R. Kanaar, et al., Nuclear dynamics of PCNA in DNA replication and repair. Mol. Cell. Biol. 25(21), 9350–9359 (2005)CrossRefGoogle Scholar
  9. C.B. He, Y.P. Hu, L.C. Yin, C. Tang, C.H. Yin, Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 31(13), 3657–3666 (2010)CrossRefGoogle Scholar
  10. B. He, P. Chen, J.Y. Yang, Y. Yun, X.C. Zhang, R.H. Yang, et al., Neuroprotective effect of 20(R)-ginsenoside Rg(3) against transient focal cerebral ischemia in rats. Neurosci. Lett. 526(2), 106–111 (2012)CrossRefGoogle Scholar
  11. K. Huang, B. Shi, W. Xu, J. Ding, Y. Yang, H. Liu, et al., Reduction-responsive polypeptide nanogel delivers antitumor drug for improved efficacy and safety. Acta Biomater. 27, 179–193 (2015)CrossRefGoogle Scholar
  12. A.K. Iyer, G. Khaled, J. Fang, H. Maeda, Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov. Today 11(17–18), 812–818 (2006)CrossRefGoogle Scholar
  13. T.K. Jain, M.A. Morales, S.K. Sahoo, D.L. Leslie-Pelecky, V. Labhasetwar, Iron oxide nanoparticles for sustained delivery of anticancer agents. Mol. Pharm. 2(3), 194–205 (2005)CrossRefGoogle Scholar
  14. K. Kataoka, A. Harada, Y. Nagasaki, Block copolymer micelles for drug delivery: Design, characterization and biological significance. Adv. Drug Deliv. Rev. 47(1), 113–131 (2001)CrossRefGoogle Scholar
  15. S.M. Kim, S.Y. Lee, D.Y. Yuk, D.C. Moon, S.S. Choi, Y. Kim, et al., Inhibition of NF-kappa B by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel. Arch. Pharm. Res. 32(5), 755–765 (2009)CrossRefGoogle Scholar
  16. C.H. Lee, J.H. Kim, A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J Ginseng Res 38(3), 161–166 (2014)CrossRefGoogle Scholar
  17. B.H. Li, J.O. Zhao, C.Z. Wang, J. Searle, T.C. He, C.S. Yuan, et al., Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53. Cancer Lett. 301(2), 185–192 (2011)CrossRefGoogle Scholar
  18. M. Li, W. Song, Z. Tang, S. Lv, L. Lin, H. Sun, et al., Nanoscaled poly(L-glutamic acid)/doxorubicin-Amphiphile complex as pH-responsive drug delivery system for effective treatment of nonsmall cell lung Cancer. ACS Appl. Mater. Interfaces 5(5), 1781–1792 (2013)CrossRefGoogle Scholar
  19. L. Li, K. Piontek, M. Ishida, M. Fausther, J.A. Dranoff, R. Fu, et al., Extracellular vesicles carry MicroRNA-195 to intrahepatic cholangiocarcinoma and improve survival in a rat model. Hepatology 65(2), 501–514 (2017)CrossRefGoogle Scholar
  20. J.N. Li, W.G. Xu, D. Li, T.J. Liu, Y.S. Zhang, J.X. Ding, et al., Locally deployable nanofiber patch for sequential drug delivery in treatment of primary and advanced Orthotopic hepatomas. ACS Nano 12(7), 6685–6699 (2018)CrossRefGoogle Scholar
  21. W.K. Liu, S.X. Xu, C.T. Che, Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. Life Sci. 67(11), 1297–1306 (2000)CrossRefGoogle Scholar
  22. J. Liu, Z. Luo, J. Zhang, T. Luo, J. Zhou, X. Zhao, et al., Hollow mesoporous silica nanoparticles facilitated drug delivery via cascade pH stimuli in tumor microenvironment for tumor therapy. Biomaterials 83, 51–65 (2016)CrossRefGoogle Scholar
  23. C. Liu, Q. Gong, T. Chen, J. Lv, Z.P. Feng, P.J. Liu, et al., Treatment with 20(S)-ginsenoside Rg3 reverses multidrug resistance in A549/DDP xenograft tumors. Oncol. Lett. 15(4), 4376–4382 (2018)Google Scholar
  24. M.X. Lu, Z.H. Fei, G.L. Zhang, Synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib in hepatocellular carcinoma by modulating PTEN/Akt signaling pathway. Biomed. Pharmacother. 97, 1282–1288 (2018)CrossRefGoogle Scholar
  25. S. Lv, M. Li, Z. Tang, W. Song, H. Sun, H. Liu, et al., Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy. Acta Biomater. 9(12), 9330–9342 (2013)CrossRefGoogle Scholar
  26. R. Meza, J. Jeon, A.G. Renehan, E.G. Luebeck, Colorectal Cancer incidence trends in the United States and United Kingdom: Evidence of right- to left-sided biological gradients with implications for screening. Cancer Res. 70(13), 5419–5429 (2010)CrossRefGoogle Scholar
  27. D.K. Monga, M.J. O'Connell, Surgical adjuvant therapy for colorectal cancer: Current approaches and future directions. Ann. Surg. Oncol. 13(8), 1021–1034 (2006)CrossRefGoogle Scholar
  28. J. Nie, W. Cheng, Y. Peng, G. Liu, Y. Chen, X. Wang, et al., Co-delivery of docetaxel and bortezomib based on a targeting nanoplatform for enhancing cancer chemotherapy effects. Drug Deliv 24(1), 1124–1138 (2017)CrossRefGoogle Scholar
  29. H.J. Park, M.J. Kim, E. Ha, J.H. Chung, Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4. Phytomedicine 15(1–2), 147–151 (2008)CrossRefGoogle Scholar
  30. S. Popat, R. Hubner, R.S. Houlston, Systematic review of microsatellite instability and colorectal cancer prognosis. J. Clin. Oncol. 23(3), 609–618 (2005)CrossRefGoogle Scholar
  31. A.T. Shaw, D.W. Kim, K. Nakagawa, T. Seto, L. Crino, M.J. Ahn, et al., Crizotinib versus chemotherapy in advanced ALK-positive lung Cancer. N. Engl. J. Med. 368(25), 2385–2394 (2013)CrossRefGoogle Scholar
  32. M.Y. Sun, Y. Ye, L. Xiao, X.Y. Duan, Y.M. Zhang, H. Zhang, Anticancer effects of ginsenoside Rg3 (review). Int. J. Mol. Med. 39(3), 507–518 (2017a)CrossRefGoogle Scholar
  33. X. Sun, R. Du, L. Zhang, G. Zhang, X. Zheng, J. Qian, et al., A pH-responsive yolk-like Nanoplatform for tumor targeted dual-mode magnetic resonance imaging and chemotherapy. ACS Nano 11(7), 7049–7059 (2017b)CrossRefGoogle Scholar
  34. R. Tong, H.H. Chiang, D.S. Kohane, Photoswitchable nanoparticles for in vivo cancer chemotherapy. Proc. Natl. Acad. Sci. U. S. A. 110(47), 19048–19053 (2013)CrossRefGoogle Scholar
  35. G. Wan, B. Chen, L. Li, D. Wang, S. Shi, T. Zhang, et al., Nanoscaled red blood cells facilitate breast cancer treatment by combining photothermal/photodynamic therapy and chemotherapy. Biomaterials 155, 25–40 (2018)CrossRefGoogle Scholar
  36. C.Z. Wang, C.S. Yuan, Potential role of ginseng in the treatment of colorectal Cancer. Am. J. Chin. Med. 36(6), 1019–1028 (2008)CrossRefGoogle Scholar
  37. M.L. Wei, Y.F. Gao, X. Li, M.J. Serpe, Stimuli-responsive polymers and their applications. Polym. Chem. 8(1), 127–143 (2017)CrossRefGoogle Scholar
  38. T.M. Xu, Y. Xin, M.H. Cui, X. Jiang, L.P. Gu, Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer. Chin. Med. J. 120(7), 584–588 (2007)CrossRefGoogle Scholar
  39. W. Xu, J. Ding, C. Xiao, L. Li, X. Zhuang, X. Chen, Versatile preparation of intracellular-acidity-sensitive oxime-linked polysaccharide-doxorubicin conjugate for malignancy therapeutic. Biomaterials 54, 72–86 (2015)CrossRefGoogle Scholar
  40. R. Yang, D.Z. Chen, M.F. Li, F.Q. Miao, P.D. Liu, Q.S. Tang, 20 (s)-ginsenoside Rg3-loaded magnetic human serum albumin nanospheres applied to HeLa cervical cancer cells in vitro. Biomed. Mater. Eng. 24(6), 1991–1998 (2014)Google Scholar
  41. Q.Y. Zhang, X.M. Kang, W.H. Zhao, Antiangiogenic effect of low-dose cyclophosphamide combined with ginsenoside Rg3 on Lewis lung carcinoma. Biochem. Biophys. Res. Commun. 342(3), 824–828 (2006)CrossRefGoogle Scholar
  42. Q. Zhang, J. Ding, C. Lv, W. Xu, X. Sun, X. Meng, Epirubicin-complexed polypeptide micelle effectively and safely treats hepatocellular carcinoma. Polymers 7(11), 2410–2430 (2015)CrossRefGoogle Scholar
  43. K. Zhao, D. Li, W. Xu, J. Ding, W. Jiang, M. Li, et al., Targeted hydroxyethyl starch prodrug for inhibiting the growth and metastasis of prostate cancer. Biomaterials 116, 82–94 (2017a)CrossRefGoogle Scholar
  44. L. Zhao, G. Chen, J. Li, Y. Fu, T.A. Mavlyutov, A. Yao, et al., An intraocular drug delivery system using targeted nanocarriers attenuates retinal ganglion cell degeneration. J. Control. Release 247, 153–166 (2017b)CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.China-Japan Union Hospital of Jilin UniversityChangchunChina
  2. 2.The First Hospital of Jilin UniversityChangchunChina

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