Tumor Biology

, Volume 37, Issue 2, pp 2703–2708 | Cite as

Enhanced anti-tumor effects of doxorubicin on glioma by entrapping in polybutylcyanoacrylate nanoparticles

  • Yuebin Zhang
  • Jia Yu
  • Lifeng Zhang
  • Jiabin Cai
  • Doute Cai
  • Chengjie Lv
Original Article

Abstract

For effective therapy for glioma, it is essential for chemotherapeutics to pass the blood-brain barrier to target glioma cells with little side effects to surrounding normal cells. In this study, we prepared doxorubicin-polybutylcyanoacrylate nanoparticles (Dox-PBCA-NP) and assessed its inhibition effects on glioma both in vitro and in vivo. Dox-PBCA-NP was prepared using the emulsion polymerization method. The size and size distribution of nanoparticles were measured by Malven laser mastersizer and the morphology was observed under transmission electron microscope. Drug loading (DL) and entrapment efficiency (EE) of doxorubicin in the nanoparticles were measured by UV spectra. The proliferation of C6 glioma cells was detected by MTT assay, and cell cycle was analyzed by flow cytometry. The expression of telomerase was detected by immunocytochemical analysis. The anti-tumor efficiency of Dox-PBCA-NP was assessed in C6 glioma intracranial implant rat model. The average diameter of NP-Dox was 120 nm, DL was 10.58 %, and EE was 87.43 %. We found that the cytotoxicity of Dox-PBCA-NP was lower than Dox in vitro. In vivo, Dox-PBCA-NP could transport more Dox into tumors compared to contralateral control, and the life span was longer than Dox. Moreover, Dox-PBCA-NP had less cardiotoxicity than Dox. Taken together, our results suggest that Dox-PBCA-NP exhibits better therapeutic effects against glioma and fewer side effects and is a potential nano-scale drug delivery system for glioma chemotherapy.

Keywords

Polybutylcyanoacrylate nanoparticles Doxorubicin Glioma Cardiotoxicity 

Notes

Compliance with ethical standards

Animal studies were approved by the Institutional Animal Care and Use Committee of Zhejiang University.

Conflicts of interest

None

References

  1. 1.
    Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY. Primary brain tumours in adults. Lancet. 2012;379(9830):1984–96.CrossRefPubMedGoogle Scholar
  2. 2.
    Jain V, Jain S, Mahajan SC. Nanomedicines based drug delivery systems for anti-cancer targeting and treatment. Curr Drug Deliv. 2015;12(2):177–91.CrossRefPubMedGoogle Scholar
  3. 3.
    Stan AC, Casares S, Radu D, Walter GF, Brumeanu TD. Doxorubicin induced cell death in highly invasive human gliomas. Anticancer Res. 1999;19(2A):941–50.PubMedGoogle Scholar
  4. 4.
    Bagherpour Doun SK, Alavi SE, Koohi Moftakhari Esfahani M, Ebrahimi Shahmabadi H, Alavi F, Hamzei S. Efficacy of cisplatin-loaded poly butyl cyanoacrylate nanoparticles on the ovarian cancer: an in vitro study. Tumour Biol. 2014;35(8):7491–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Chaudhari KR, Ukawala M, Manjappa AS, Kumar A, Mundada PK, Mishra AK, et al. Opsonization, biodistribution, cellular uptake and apoptosis study of PEGylated PBCA nanoparticle as potential drug delivery carrier. Pharm Res. 2012;29(1):53–68.CrossRefPubMedGoogle Scholar
  6. 6.
    Tian XH, Lin XN, Wei F, Feng W, Huang ZC, Wang P, et al. Enhanced brain targeting of temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles. Int J Nanomedicine. 2011;6:445–52.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Ebrahimi Shahmabadi H, Movahedi F, Koohi Moftakhari Esfahani M, Alavi SE, Eslamifar A, Mohammadi Anaraki G, et al. Efficacy of cisplatin-loaded polybutyl cyanoacrylate nanoparticles on the glioblastoma. Tumour Biol. 2014;35(5):4799–806.CrossRefPubMedGoogle Scholar
  8. 8.
    Liu G, Shen H, Mao J, Zhang L, Jiang Z, Sun T, et al. Transferrin modified graphene oxide for glioma-targeted drug delivery: in vitro and in vivo evaluations. ACS Appl Mater Interfaces. 2013;5(15):6909–14.CrossRefPubMedGoogle Scholar
  9. 9.
    Liu G, Mao J, Jiang Z, Sun T, Hu Y, Jiang Z, et al. Transferrin-modified doxorubicin-loaded biodegradable nanoparticles exhibit enhanced efficacy in treating brain glioma-bearing rats. Cancer Biother Radiopharm. 2013;28(9):691–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Mao J, Li A, Zhao L, Gao L, Xu W, Hong X, et al. PEG-PLGA nanoparticles entrapping doxorubicin reduced doxorubicin-induced cardiotoxicity in rats. Adv Mater Res. 2014;912–914:263–8.CrossRefGoogle Scholar
  11. 11.
    Sayed-Ahmed MM, Khattab MM, Gad MZ, Osman AM. Increased plasma endothelin-1 and cardiac nitric oxide during doxorubicin-induced cardiomyopathy. Pharmacol Toxicol. 2001;89(3):140–4.CrossRefPubMedGoogle Scholar
  12. 12.
    Li M, Deng H, Peng H, Wang Q. Functional nanoparticles in targeting glioma diagnosis and therapies. J Nanosci Nanotechnol. 2014;14(1):415–32.CrossRefPubMedGoogle Scholar
  13. 13.
    Pardridge WM. BBB-genomics: creating new openings for brain-drug targeting. Drug Discov Today. 2001;6(8):381–3.CrossRefPubMedGoogle Scholar
  14. 14.
    De Juan BS, Von Briesen H, Gelperina SE, Kreuter J. Cytotoxicity of doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles in rat glioma cell lines using different assays. J Drug Target. 2006;14(9):614–22.CrossRefPubMedGoogle Scholar
  15. 15.
    Ambruosi A, Khalansky AS, Yamamoto H, Gelperina SE, Begley DJ, Kreuter J. Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastoma-bearing rats. J Drug Target. 2006;14(2):97–105.CrossRefPubMedGoogle Scholar
  16. 16.
    Mitra A, Lin S. Effect of surfactant on fabrication and characterization of paclitaxel-loaded polybutylcyanoacrylate nanoparticulate delivery systems. J Pharm Pharmacol. 2003;55(7):895–902.CrossRefPubMedGoogle Scholar
  17. 17.
    Karimi G, Ramezani M, Abdi A. Protective effects of lycopene and tomato extract against doxorubicin-induced cardiotoxicity. Phytother Res. 2005;19(10):912–4.CrossRefPubMedGoogle Scholar
  18. 18.
    Hydock DS, Lien CY, Schneider CM, Hayward R. Exercise preconditioning protects against doxorubicin-induced cardiac dysfunction. Med Sci Sports Exerc. 2008;40(5):808–17.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yuebin Zhang
    • 1
  • Jia Yu
    • 2
  • Lifeng Zhang
    • 1
  • Jiabin Cai
    • 1
  • Doute Cai
    • 1
  • Chengjie Lv
    • 1
  1. 1.Department of General SurgeryChildren’s Hospital Zhejiang University School of MedicineHangzhouChina
  2. 2.Department of ICUChildren’s Hospital Zhejiang University School of MedicineHangzhouChina

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