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Preparation, characterization, and in vitro targeted delivery of folate-conjugated 2-methoxyestradiol-loaded bovine serum albumin nanoparticles

  • Nan Zhang
  • Yadan Xia
  • Xiaojing Guo
  • Pei Wang
  • Shujuan Yan
  • Chunyun Lu
  • Danhua Cao
  • Zhenzhong Zhang
Research Paper

Abstract

The aim of this study was to prepare a novel targeting nano drug delivery system of 2-methoxyestradiol (2-ME) based on the folic acid-modified bovine serum albumin, in order to improve the clinical application disadvantages and antitumor effect of 2-ME. In this study, 2-methoxyestradiol-loaded albumin nanoparticles (2-ME-BSANPs) were prepared by desolvation method, and then the activated folic acid was conjugated to 2-ME-BSANPs by covalent attachment (2-ME-FA-BSANPs). The size and zeta potential of 2-ME-FA-BSANPs were about 208.8 ± 5.1 nm and −32.70 ± 1.01 mV, respectively. 2-ME loading efficiency and loading amount of the nanoparticles were 80.49 ± 3.80 and 10.25 ± 1.59 %, respectively. SEM images indicated that 2-ME-FA-BSANPs were of a round shape, similar uniform size, and smooth surface. Studies on drug release indicated that 2-ME-FA-BSANPs had the properties of sustained and controlled release, which provided them with the ability to fight continually against cancer cells. Internalization analysis demonstrated that 2-ME-FA-BSANPs-targeting drug delivery system could get efficiently transferred into the cells through the folic acid-mediated endocytosis, leading to higher apoptosis and affording higher antitumor efficacy against SMMC-7721 cells in vitro compared with 2-ME alone. Furthermore, the cell-cycle arrest of 2-ME-FA-BSANPs on the SMMC-7721 cells occurred at G2/M phase, and 2-ME-FA-BSANPs did not change the inhibition of the tumor mechanisms of 2-ME. Based on these results, it was concluded that albumin nanoparticles could be the promising nano carrier for 2-ME, and 2-ME-FA-BSANPs-targeting drug delivery system may be promising candidate for providing high treatment efficacy with minimal side effects in future cancer therapy.

Keywords

2-Methoxyestradiol Bovine serum albumin Folic acid Targeting delivery system Nanomedicine 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81273451).

References

  1. Birnbaum DT, Kosmala JD, Brannon-Peppas L (2000) Optimization of preparation techniques for poly (lactic acid-co-glycolic acid) nanoparticles. J Nanopart Res 2:173–181. doi: 10.1023/A:1010038908767 CrossRefGoogle Scholar
  2. Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 60(15):1615–1626. doi: 10.1016/j.addr.2008.08.005 CrossRefGoogle Scholar
  3. Chen CQ, Zhang HJ, Hou L, Shi JJ, Wang L, Zhang CF, Zhang MY, Zhang HL, Shi XF, Li HX, Zhang ZZ (2013) Single-walled carbon nanotubes mediated neovascularity targeted antitumor drug delivery system. J Pharm Pharm Sci 16:41–50. www.cspsCanada.org Google Scholar
  4. Chuang VTG, Kragh-Hansen U, Otagiri M (2002) Pharmaceutical strategies utilizing recombinant human serum albumin. Pharm Res 19:569–577. doi: 10.1023/A:1015396825274 CrossRefGoogle Scholar
  5. Dosio F, Arpico S, Stella B, Brusa P, Cattel L (2009) Folate-mediated targeting of albumin conjugates of paclitaxel obtained through a heterogeneous phase system. Int J Pharm 382:117–123. doi: 10.1016/j.ijpharm.2009.08.018 CrossRefGoogle Scholar
  6. Elzoghby AO, Samy WM, Elgindy NA (2012) Albumin-based nanoparticles as potential controlled release drug delivery systems. J Control Release 157:168–182. doi: 10.1016/j.jconrel.2011.07.031 CrossRefGoogle Scholar
  7. Gong J, Huo MR, Zhou JP, Zhang Y, Peng XL, Yu D, Zhang H, Li J (2009) Synthesis, characterization, drug-loading capacity and safety of novel octyl modified serum albumin micelles. Int J Pharm 376:161–168. doi: 10.1016/j.ijpharm.2009.04.033 CrossRefGoogle Scholar
  8. Gruner BA, Weitman SD (1999) The folate receptor as a potential therapeutic anticancer target. Invest New Drugs 16:205–219. doi: 10.1023/A:1006147932159 CrossRefGoogle Scholar
  9. Guo XH, Xing YB, Mei Q, Zhang HL, Zhang ZZ, Cui FD (2008) Preparation and cytotoxicity of 2-methoxyestradiol-loaded solid lipid nanoparticles. Anticancer Drugs 23:185–190. doi: 10.1097/CAD.0b013e32834cf8d0 CrossRefGoogle Scholar
  10. Hao HP, Ma QM, Huang C, He F, Yao P (2013) Preparation, characterization, and in vivo, evaluation of doxorubicin loaded BSA nanoparticles with folic acid modified dextran surface. Int J Pharm 444:77–84. doi: 10.1016/j.ijpharm.2013.01.041 CrossRefGoogle Scholar
  11. Huang S, Wan Y, Wang Z, Jiliang W (2013) Folate-conjugated chitosan–polylactide nanoparticles for enhanced intracellular uptake of anticancer drug. J Nanopart Res 15:2096. doi: 10.1007/s11051-013-2096-1 CrossRefGoogle Scholar
  12. Langer K, Balthasar S, Vogel V, Dinauer N, von Briesen H, Schubert D (2003) Optimization of the preparation process for human serum albumin (HSA) nanoparticles. Int J Pharm 257:169–180. doi: 10.1016/S0378-5173(03)00134-0 CrossRefGoogle Scholar
  13. Lee S, Murthy N (2007) Targeted delivery of catalase and superoxide dismutase to macrophages using folate. Biochem Biophys Res Commun 360:275–279. doi: 10.1016/j.bbrc.2007.06.054 CrossRefGoogle Scholar
  14. Li FQ, Su H, Wang J, Liu YJ, Zhu QG, Fei YB, Pan YH, Hu JH (2008) Preparation and characterization of sodium ferulate entrapped bovine serum albumin nanoparticles for live targeting. Int J Pharm 349:274–282. doi: 10.1016/j.ijpharm.2007.08.001 CrossRefGoogle Scholar
  15. Lu Y, Low PS (2002) Folate-mediated delivery of macromolecular anticancer therapeutic agents. Adv Drug Deliv Rev 54:675–693. doi: 10.1016/j.addr.2012.09020 CrossRefGoogle Scholar
  16. Maruyama K (2011) Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Deliv Rev 63(3):161–169. doi: 10.1016/j.addr.2010.09.003 CrossRefGoogle Scholar
  17. Najafabadi AH, Abdouss M, Faghihi S (2014) Preparation and characterization of PEGylated chitosan nanocapsules as a carrier for pharmaceutical application. J Nanopart Res 16:2312. doi: 10.1007/s11051-014-2312-7 CrossRefGoogle Scholar
  18. Patil GV (2003) Biopolymer albumin for diagnosis and in drug delivery. Drug Dev Res 58:219–247. doi: 10.1002/ddr.10157 CrossRefGoogle Scholar
  19. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2(12):751–760. doi: 10.1038/nnano.2007.387 CrossRefGoogle Scholar
  20. Qi JN, Yao P, He F, Yu CL, Huang C (2010) Nanoparticles with dextran/chitosan shell and BSA/chitosan core-doxorubicin loading and delivery. Int J Pharm 393:176–184. doi: 10.1016/j.ijpharm.2010.03.063 CrossRefGoogle Scholar
  21. Rahimnejad M, Jahanshahi M, Najafpour GD (2006) Production of biological nanoparticles from bovine serum albumin for drug delivery. Afr J Biotechnol 5(2006):1918–1923. doi: 10.4314/ajbv5i20.55912 Google Scholar
  22. Sabharanjak S, Mayor S (2004) Folate receptor endocytosis and trafficking. Adv Drug Deliv Rev 56:1099–1109. doi: 10.1016/j.addr.2004.01.010 CrossRefGoogle Scholar
  23. Shi JJ, Zhang HL, Wang L, Li LL, Wang HH, Wang ZZ, Li Z, Chen CQ, Hou L, Zhang CF, Zhang ZZ (2013) PEI-derivatized fullerene drug delivery using folate as a homing device targeting to tumor. Biomaterials 34:251–261. doi: 10.1016/j.biomaterials.2012.09.039 CrossRefGoogle Scholar
  24. Sutherland TE, Anderson RL, Hughes RA, Altmann E, Schuliga M, Ziogas J et al (2007) 2-Methoxy estradiol-a unique blend of activities generating a new class of anti-tumour/anti-inflammatory agents. Drug Discov Today 12:577–584. doi: 10.1016/j.drudis.2007.05.005 CrossRefGoogle Scholar
  25. Wilbur DS, Chyan MK, Hamlin DK et al (2004) Reagents for astatination of biomolecules: comparison of the in vivo distribution and stability of some radioiodinated/astatinated benzamidyl and nido-carboranyl compounds. Bioconjug Chem 15:203–223. doi: 10.1021/bc034175k CrossRefGoogle Scholar
  26. Yang L, Cui F, Cun DM, Tao A, Shi K, Lin WH (2007) Preparation, characterization and biodistribution of the lactone form of 10-hydroxycamptothecin (HCPT)-loaded bovine serum albumin (BSA) nanoparticles. Int J Pharm 340:163–172. doi: 10.1016/j.ijpharm.2007.03.028 CrossRefGoogle Scholar
  27. Zhang DW, Dougherty SA, Liang JL (2011) Fabrication of bovine serum albumin nanotubes through template-assisted layer by layer assembly. J Nanopart Res 13:1563–1571. doi: 10.1007/s1-011-0254-x CrossRefGoogle Scholar
  28. Zhang L, Hou S, Mao S, Wei D, Song X, Lu Y (2004) Uptake folate-conjugated albumin nanoparticles to the SKOV3 cells. Int J Pharm 287:155–162. doi: 10.1016/j.ijpharm.2004.08.015 CrossRefGoogle Scholar
  29. Zhao DM, Zhao XH, Zu YG, Li JL, Zhang Y, Jiang R, Zhang ZH (2010) Preparation, characterization, and in vitro targeted delivery of folate-decorated paclitaxel-loaded bovine serum albumin nanoparticles. Int J Nanomed 5:669–677. doi: 10.2147/IJN.S12918 Google Scholar
  30. Zheng Y, Song SG, Darby M et al (2009) Preparation and characterization of folate-poly(ethylene glycol)-grafted-trimethylchitosan for intracellular transport of protein through folate receptor-mediated endocytosis. J Biotechnol 145:47–53. doi: 10.1016/j.jbiotec.2009.09.007 CrossRefGoogle Scholar
  31. Zhu XL, Huang SN, Xie YX et al (2014) Folic acid mediated solid lipid nanocarriers loaded with docetaxel and oxidized single-walled carbon nanotubes. J Nanopart Res 16:2207. doi: 10.1007/s11051-013-2207-z CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Nan Zhang
    • 1
  • Yadan Xia
    • 1
  • Xiaojing Guo
    • 1
  • Pei Wang
    • 1
  • Shujuan Yan
    • 1
  • Chunyun Lu
    • 1
  • Danhua Cao
    • 1
  • Zhenzhong Zhang
    • 1
  1. 1.School of Pharmaceutical SciencesZhengzhou UniversityZhengzhouPeople’s Republic of China

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