Journal of Materials Science

, Volume 54, Issue 11, pp 8613–8626 | Cite as

Biotin-modified bovine serum albumin nanoparticles as a potential drug delivery system for paclitaxel

  • Danfeng Wang
  • Na LiangEmail author
  • Yoshiaki Kawashima
  • Fude Cui
  • Pengfei Yan
  • Shaoping SunEmail author
Materials for life sciences


This study proposed a novel injectable nanocarrier for paclitaxel (PTX) based on biotin-modified bovine serum albumin (BSA). First, the biotin-modified BSA (biotin-BSA) was successfully synthesized and characterized by FT-IR analysis. Then, the PTX-loaded biotin-BSA nanoparticles (NPs) were prepared by disulfide bond reducing method and stabilized through the formation of intermolecular disulfide bonds. The influence of solution pH, glutathione concentration, temperature and organic solvent on the formation of NPs was studied. Under the optimized conditions, the PTX-loaded NPs had a mean diameter of 163 nm with zeta potential of − 35 mV. Transmission electron microscopy analysis showed that the NPs were sphere in shape and had a narrow size distribution. XRD and DSC spectra confirmed the successful encapsulation of PTX in the NPs in an amorphous state. The MTT assay verified that the in vitro cytotoxicity of PTX-loaded biotin-BSA NPs to biotin receptor-positive MCF-7 cells was a little higher than that of Taxol®. The cellular uptake experiments by flow cytometry demonstrated the biotin receptor-mediated endocytosis of biotin-BSA NPs. It can be concluded that the PTX-loaded biotin-BSA NPs were a promising drug delivery carrier for PTX.



The financial support from the National Natural Science Foundation of China (No. 51403057), Heilongjiang Natural Science Foundation (No. E2018052), Research and Development Project of Scientific and Technological Achievements for Colleges and Universities of Heilongjiang Province (No. TSTAU-R2018023), Harbin Science and Technology Innovation Talents Special Fund Project (Nos. 2016RQQXJ097 and 2016RQQXJ131) and the Doctoral Scientific Research Startup Foundation of Harbin Normal University (No. XKB201304) is gratefully acknowledged.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.


  1. 1.
    Dian L, Hu Y, Lin J, Zhang J, Yan Y, Cui Y, Su Z, Lu W (2018) Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration. Int J Nanomed 13:719–731Google Scholar
  2. 2.
    Elzoghby AO, Samy WM, Elgindy NA (2012) Albumin-based nanoparticles as potential controlled release drug delivery systems. J Control Release 157(2):168–182Google Scholar
  3. 3.
    Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A, Tao C, De T, Beals B, Dykes D, Noker P, Yao R, Labao E, Hawkins M, Soon-Shiong P (2006) Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res 12(4):1317–1324Google Scholar
  4. 4.
    Salehiabar M, Nosrati H, Javani E, Aliakbarzadeh F, Kheiri Manjili H, Davaran S, Danafar H (2018) Production of biological nanoparticles from bovine serum albumin as controlled release carrier for curcumin delivery. Int J Biol Macromol 115:83–89Google Scholar
  5. 5.
    Crisante F, Francolini I, Bellusci M, Martinelli A, D’Ilario L, Piozzi A (2009) Antibiotic delivery polyurethanes containing albumin and polyallylamine nanoparticles. Eur J Pharm Sci 36(4):555–564Google Scholar
  6. 6.
    Kushwah V, Katiyar SS, Dora CP, Kumar Agrawal A, Lamprou DA, Gupta RC, Jain S (2018) Co-delivery of docetaxel and gemcitabine by anacardic acid modified self-assembled albumin nanoparticles for effective breast cancer management. Acta Biomater 73:424–436Google Scholar
  7. 7.
    Fürst W, Banerjee A (2005) Release of glutaraldehyde from an albumin-glutaraldehyde tissue adhesive causes significant in vitro and in vivo toxicity. Ann Thorac Surg 79(5):1522–1528Google Scholar
  8. 8.
    Wang W, Huang Y, Zhao S, Shao T, Cheng Y (2013) Human serum albumin (HSA) nanoparticles stabilized with intermolecular disulfide bonds. Chem Commun 49(22):2234–2236Google Scholar
  9. 9.
    Shi H, Cheng Q, Yuan S, Ding X, Liu Y (2015) Human serum albumin conjugated nanoparticles for pH and redox-responsive delivery of a prodrug of cisplatin. Chem Eur J 21(46):16547–16554Google Scholar
  10. 10.
    Hong R, Han G, Fernández JM, B-j Kim, Forbes NS, Rotello VM (2006) Glutathione-mediated delivery and release using monolayer protected nanoparticle carriers. J Am Chem Soc 128(4):1078–1079Google Scholar
  11. 11.
    Jiang L, Xu Y, Liu Q, Tang Y, Ge L, Zheng C, Zhu J, Liu J (2013) A nontoxic disulfide bond reducing method for lipophilic drug-loaded albumin nanoparticle preparation: formation dynamics, influencing factors and formation mechanisms investigation. Int J Pharm 443(1):80–86Google Scholar
  12. 12.
    Gazzano E, Rolando B, Chegaev K, Salaroglio IC, Kopecka J, Pedrini I, Saponara S, Sorge M, Buondonno I, Stella B, Marengo A, Valoti M, Brancaccio M, Fruttero R, Gasco A, Arpicco S, Riganti C (2018) Folate-targeted liposomal nitrooxy-doxorubicin: an effective tool against P-glycoprotein-positive and folate receptor-positive tumors. J Control Release 270:37–52Google Scholar
  13. 13.
    Chen X, Sun H, Hu J, Han X, Liu H, Hu Y (2017) Transferrin gated mesoporous silica nanoparticles for redox-responsive and targeted drug delivery. Colloid Surface B 152:77–84Google Scholar
  14. 14.
    Alibakhshi A, Abarghooi Kahaki F, Ahangarzadeh S, Yaghoobi H, Yarian F, Arezumand R, Ranjbari J, Mokhtarzadeh A, de la Guardia M (2017) Targeted cancer therapy through antibody fragments-decorated nanomedicines. J Control Release 268:323–334Google Scholar
  15. 15.
    Kim SK, Foote MB, Huang L (2012) The targeted intracellular delivery of cytochrome  C protein to tumors using lipid-apolipoprotein nanoparticles. Biomaterials 33(15):3959–3966Google Scholar
  16. 16.
    Yang W, Wang M, Ma L, Li H, Huang L (2014) Synthesis and characterization of biotin modified cholesteryl pullulan as a novel anticancer drug carrier. Carbohyd Polym 99:720–727Google Scholar
  17. 17.
    Navid N, Navid G, Mohsen A, Fatemeh A, Reza KM, Rassoul D (2016) Biotin/folate-decorated human serum albumin nanoparticles of docetaxel: comparison of chemically conjugated nanostructures and physically loaded nanoparticles for targeting of breast cancer. Chem Biol Drug Des 87(1):69–82Google Scholar
  18. 18.
    Taheri A, Dinarvand R, Nouri FS, Khorramizadeh MR, Borougeni AT, Mansoori P, Atyabi F (2011) Use of biotin targeted methotrexate-human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy. Int J Nanomed 6:1863–1874Google Scholar
  19. 19.
    Liang N, Sun S, Li X, Piao H, Piao H, Cui F, Fang L (2012) α-Tocopherol succinate-modified chitosan as a micellar delivery system for paclitaxel: preparation, characterization and in vitro/in vivo evaluations. Int J Pharm 423(2):480–488Google Scholar
  20. 20.
    Liu L, Bi Y, Zhou M, Chen X, He X, Zhang Y, Sun T, Ruan C, Chen Q, Wang H, Jiang C (2017) Biomimetic human serum albumin nanoparticle for efficiently targeting therapy to metastatic breast cancers. ACS Appl Mater Interfaces 9(8):7424–7435Google Scholar
  21. 21.
    Park C, Vo CL-N, Kang T, Oh E, Lee B-J (2015) New method and characterization of self-assembled gelatin-oleic nanoparticles using a desolvation method via carbodiimide/N-hydroxysuccinimide (EDC/NHS) reaction. Eur J Pharm Biopharm 89:365–373Google Scholar
  22. 22.
    Bronze-Uhle ES, Costa BC, Ximenes VF, Lisboa-Filho PN (2017) Synthetic nanoparticles of bovine serum albumin with entrapped salicylic acid. Nanotechnol Sci Appl 10:11–21Google Scholar
  23. 23.
    Bourassa P, Hasni I, Tajmir-Riahi HA (2011) Folic acid complexes with human and bovine serum albumins. Food Chem 129(3):1148–1155Google Scholar
  24. 24.
    Lin T, Zhao P, Jiang Y, Tang Y, Jin H, Pan Z, He H, Yang VC, Huang Y (2016) Blood–brain-barrier-penetrating albumin nanoparticles for biomimetic drug delivery via albumin-binding protein pathways for antiglioma therapy. ACS Nano 10(11):9999–10012Google Scholar
  25. 25.
    Yang Z, Gong W, Wang Z, Li B, Li M, Xie X, Zhang H, Yang Y, Li Z, Li Y, Yu F, Mei X (2015) A novel drug-polyethylene glycol liquid compound method to prepare 10-hydroxycamptothecin loaded human serum albumin nanoparticle. Int J Pharm 490(1):412–428Google Scholar
  26. 26.
    Kayani Z, Firuzi O, Bordbar A-K (2018) Doughnut-shaped bovine serum albumin nanoparticles loaded with doxorubicin for overcoming multidrug-resistant in cancer cells. Int J Biol Macromol 107:1835–1843Google Scholar
  27. 27.
    Boonyaratanakornkit BB, Park CB, Clark DS (2002) Pressure effects on intra- and intermolecular interactions within proteins. Biochim Biophys Acta 1595(1):235–249Google Scholar
  28. 28.
    Grossmann L, Ebert S, Hinrichs J, Weiss J (2018) Effect of precipitation, lyophilization, and organic solvent extraction on preparation of protein-rich powders from the microalgae Chlorella protothecoides. Algal Res 29:266–276Google Scholar
  29. 29.
    Albanese A, Tang PS, Chan WCW (2012) The Effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng 14(1):1–16Google Scholar
  30. 30.
    Prabha G, Raj V (2017) Sodium alginate–polyvinyl alcohol–bovin serum albumin coated Fe3O4 nanoparticles as anticancer drug delivery vehicle: doxorubicin loading and in vitro release study and cytotoxicity to HepG2 and L02 cells. Mater Sci Eng C Mater Biol Appl 79:410–422Google Scholar
  31. 31.
    Kim C, Lee SC, Kang SW, Kwon IC, Kim Y-H, Jeong SY (2000) Synthesis and the micellar characteristics of poly(ethylene oxide)-deoxycholic acid conjugates. Langmuir 16(11):4792–4797Google Scholar
  32. 32.
    Ren WX, Han J, Uhm S, Jang YJ, Kang C, Kim J-H, Kim JS (2015) Recent development of biotin conjugation in biological imaging, sensing, and target delivery. Chem Commun 51(52):10403–10418Google Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Key Laboratory of Chemical Engineering Process and Technology for High-Efficiency Conversion, College of Heilongjiang Province, School of Chemistry and Material ScienceHeilongjiang UniversityHarbinChina
  2. 2.Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, Heilongjiang Province, College of Chemistry and Chemical EngineeringHarbin Normal UniversityHarbinChina
  3. 3.Department of Pharmaceutical Engineering, School of PharmacyAichi Gakuin UniversityNagoyaJapan
  4. 4.School of PharmacyShenyang Pharmaceutical UniversityShenyangChina

Personalised recommendations