Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Effect of Podophyllotoxin Conjugated Stearic Acid Grafted Chitosan Oligosaccharide Micelle on Human Glioma Cells

  • Wang, Geng Huan (Department of Neurosurgery, The Second Affiliated Hospital of Jiaxing University) ;
  • Shen, He Ping (Department of Neurosurgery, The Second Affiliated Hospital of Jiaxing University) ;
  • Huang, Xuan (Department of Pharmacy, Medical College, Jiaxing University) ;
  • Jiang, Xiao Hong (Department of Pharmacy, Medical College, Jiaxing University) ;
  • Jin, Cheng Sheng (Department of Neurosurgery, The Second Affiliated Hospital of Jiaxing University) ;
  • Chu, Zheng Min (Department of Neurosurgery, The Second Affiliated Hospital of Jiaxing University)
  • Received : 2019.10.17
  • Accepted : 2019.12.27
  • Published : 2020.11.01
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Abstract

Objective : To study the physiochemical characteristics of podophyllotoxin (PPT) conjugated stearic acid grafted chitosan oligosaccharide micelle (PPT-CSO-SA), and evaluate the ability of the potential antineoplastic effects against glioma cells. Methods : PPT-CSO-SA was prepared by a dialysis method. The quality of PPT-CSO-SA including micellar size, zeta potential, drug encapsulation efficiency and drug release profiles was evaluated. Glioma cells were cultured and treated with PPT and PPT-CSO-SA. The ability of glioma cells to uptake PPT-CSO-SA was observed. The proliferation of glioma cells was determined by 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The apoptosis and morphology of U251 cells were observed by 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) dye staining. Cell cycle analysis was performed by flow cytometry. The migration ability of U251 cells was determined by wound healing test. Results : PPT-CSO-SA had nano-level particle size and sustained release property. The encapsulation efficiency of drug reached a high level. The cellular uptake percentage of PPT in glioma cells was lower than that of PPT-CSO-SA (p<0.05). The inhibitory effect of PPT-CSO-SA on glioma cells proliferation was significantly stronger than that of PPT (p<0.05). The morphologic change of apoptosis cell such as shrinkage, karyorrhexis and karyopyknosis were observed. The percentage of U251 cells in G2/M phase increased significantly in the PPT-CSO-SA group compared with PPT group (p<0.05). Compared with the PPT group, the cell migration ability of the PPT-CSO-SA group was significantly inhibited after 12 and 24 hours (p<0.05). Conclusion : PPT-CSO-SA can effectively enhance the glioma cellular uptake of drugs, inhibit glioma cells proliferation and migration, induce G2/M phase arrest of them, and promote their apoptosis. It may be a promising anti-glioma nano-drug.

Keywords

References

  1. Castro A, del Corral JM, Gordaliza M, Grande C, Gomez-Zurita A, Garcia-Gravalos D, et al. : Synthesis and cytotoxicity of podophyllotoxin analogues modified in the A ring. Eur J Med Chem 38 : 65-74, 2003 https://doi.org/10.1016/S0223-5234(02)00007-7
  2. De Campos AM, Sanchez A, Alonso MJ : Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int J Pharm 224 : 159-168, 2001 https://doi.org/10.1016/S0378-5173(01)00760-8
  3. Desbene S, Giorgi-Renault S : Drugs that inhibit tubulin polymerization: the particular case of podophyllotoxin and analogues. Curr Med Chem Anticancer Agents 2 : 71-90, 2002 https://doi.org/10.2174/1568011023354353
  4. Ellingson BM, Cloughesy TF, Zaw T, Lai A, Nghiemphu PL, Harris R, et al. : Functional diffusion maps (fDMs) evaluated before and after radiochemotherapy predict progression-free and overall survival in newly diagnosed glioblastoma. Neuro Oncol 14 : 333-343, 2012 https://doi.org/10.1093/neuonc/nor220
  5. Felix CA : Secondary leukemias induced by topoisomerase-targeted drugs. Biochim Biophys Acta 1400 : 233-255, 1998 https://doi.org/10.1016/S0167-4781(98)00139-0
  6. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, et al. : A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol 5 Suppl 2 : 91-95, 1994
  7. Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC : Block copolymer micelles: preparation, characterization and application in drug delivery. J Control Release 109 : 169-188, 2005 https://doi.org/10.1016/j.jconrel.2005.09.034
  8. Gordaliza M, Garcia PA, del Corral JM, Castro MA, Gomez-Zurita MA : Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. Toxicon 44 : 441-459, 2004 https://doi.org/10.1016/j.toxicon.2004.05.008
  9. Hu FQ, Liu LN, Du YZ, Yuan H : Synthesis and antitumor activity of doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles. Biomaterials 30 : 6955-6963, 2009 https://doi.org/10.1016/j.biomaterials.2009.09.008
  10. Hu FQ, Ren GF, Yuan H, Du YZ, Zeng S : Shell cross-linked stearic acid grafted chitosan oligosaccharide self-aggregated micelles for controlled release of paclitaxel. Colloids Surf B Biointerfaces 50 : 97-103, 2006 https://doi.org/10.1016/j.colsurfb.2006.04.009
  11. Hu FQ, Zhao MD, Yuan H, You J, Du YZ, Zeng S : A novel chitosan oligosaccharide-stearic acid micelles for gene delivery: properties and in vitro transfection studies. Int J Pharm 315 : 158-166, 2006 https://doi.org/10.1016/j.ijpharm.2006.02.026
  12. Huang X, Huang X, Jiang XH, Hu FQ, Du YZ, Zhu QF, et al. : In vitro antitumour activity of stearic acid-g-chitosan oligosaccharide polymeric micelles loading podophyllotoxin. J Microencapsul 29 : 1-8, 2012 https://doi.org/10.3109/02652048.2011.621551
  13. Jansen M, Yip S, Louis DN : Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers. Lancet Neurol 9 : 717-726, 2010 https://doi.org/10.1016/S1474-4422(10)70105-8
  14. Lara PN, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, et al. : Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol 27 : 2530-2535, 2009 https://doi.org/10.1200/JCO.2008.20.1061
  15. Li SD, Huang L : Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm 5 : 496-504, 2008 https://doi.org/10.1021/mp800049w
  16. Lopez-Perez JL, del Olmo E, de Pascual-Teresa B, Abad A, San Feliciano A : Synthesis and cytotoxicity of hydrophobic esters of podophyllotoxins. Bioorg Med Chem Lett 14 : 1283-1286, 2004 https://doi.org/10.1016/j.bmcl.2003.12.039
  17. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. : The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 : 97-109, 2007 https://doi.org/10.1007/s00401-007-0243-4
  18. Moreira JN, Gaspar R, Allen TM : Targeting Stealth liposomes in a murine model of human small cell lung cancer. Biochim Biophys Acta 1515 : 167-176, 2001 https://doi.org/10.1016/S0005-2736(01)00411-4
  19. Pedersen-Bjergaard J : Radiotherapy- and chemotherapy-induced myelodysplasia and acute myeloid leukemia. A review. Leuk Res 16 : 61-65, 1992 https://doi.org/10.1016/0145-2126(92)90102-D
  20. Qin L, Xue M, Wang W, Zhu R, Wang S, Sun J, et al. : The in vitro and in vivo anti-tumor effect of layered double hydroxides nanoparticles as delivery for podophyllotoxin. Int J Pharm 388 : 223-230, 2010 https://doi.org/10.1016/j.ijpharm.2009.12.044
  21. Sackett DL : Podophyllotoxin, steganacin and combretastatin: natural products that bind at the colchicine site of tubulin. Pharmacol Ther 59 : 163-228, 1993 https://doi.org/10.1016/0163-7258(93)90044-E
  22. Schonbrunn E, Phlippen W, Trinczek B, Sack S, Eschenburg S, Mandelkow EM, et al. : Crystallization of a macromolecular ring assembly of tubulin liganded with the anti-mitotic drug podophyllotoxin. J Struct Biol 128 : 211-215, 1999 https://doi.org/10.1006/jsbi.1999.4183
  23. Stummer W, Meinel T, Ewelt C, Martus P, Jakobs O, Felsberg J, et al. : Prospective cohort study of radiotherapy with concomitant and adjuvant temozolomide chemotherapy for glioblastoma patients with no or minimal residual enhancing tumor load after surgery. J Neurooncol 108 : 89-97, 2012 https://doi.org/10.1007/s11060-012-0798-3
  24. Venishetty VK, Komuravelli R, Kuncha M, Sistla R, Diwan PV : Increased brain uptake of docetaxel and ketoconazole loaded folate-grafted solid lipid nanoparticles. Nanomedicine 9 : 111-121, 2013 https://doi.org/10.1016/j.nano.2012.03.003
  25. You J, Hu FQ, Du YZ, Yuan H : Polymeric micelles with glycolipid-like structure and multiple hydrophobic domains for mediating molecular target delivery of paclitaxel. Biomacromolecules 8 : 2450-2456, 2007 https://doi.org/10.1021/bm070365c
  26. Zhan C, Lu W : The blood-brain/tumor barriers: challenges and chances for malignant gliomas targeted drug delivery. Curr Pharm Biotechnol 13 : 2380-2387, 2012 https://doi.org/10.2174/138920112803341798
  27. Zhang L, Wu X, Xu T, Luo C, Qian J, Lu Y : Chemotherapy plus radiotherapy versus radiotherapy alone in patients with anaplastic glioma: a systematic review and meta-analysis. J Cancer Res Clin Oncol 139 : 719-726, 2013 https://doi.org/10.1007/s00432-013-1387-3
  28. Zhu RR, Qin LL, Wang M, Wu SM, Wang SL, Zhang R, et al. : Preparation, characterization, and anti-tumor property of podophyllotoxinloaded solid lipid nanoparticles. Nanotechnology 20 : 055702, 2009 https://doi.org/10.1088/0957-4484/20/5/055702