Skip to main content

Glucose-conjugated chitosan nanoparticles for targeted drug delivery and their specific interaction with tumor cells

Abstract

A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles (GCNPs), was developed for specific recognition and interaction with glucose transporters (Gluts) over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan (CS), and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of (187.9 ± 3.8) nm and a zeta potential of (− 15.43 ± 0.31) mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin (DOX) could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-loaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline (pH 7.4). In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4–5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.

This is a preview of subscription content, access via your institution.

References

  1. [1]

    Chen C, Yu C H, Cheng Y C, et al. Biodegradable nanoparticles of amphiphilic triblock copolymers based on poly(3-hydroxybutyrate) and poly(ethylene glycol) as drug carriers. Biomaterials, 2006, 27(27): 4804–4814

    Article  Google Scholar 

  2. [2]

    Haley B, Frenkel E. Nanoparticles for drug delivery in cancer treatment. Urologic Oncology, 2008, 26(1): 57–64

    Article  Google Scholar 

  3. [3]

    Malam Y, Loizidou M, Seifalian A M. Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends in Pharmacological Sciences, 2009, 30(11): 592–599

    Article  Google Scholar 

  4. [4]

    Byrne J D, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Advanced Drug Delivery Reviews, 2008, 60(15): 1615–1626

    Article  Google Scholar 

  5. [5]

    Sudimack J, Lee R J. Targeted drug delivery via the folate receptor. Advanced Drug Delivery Reviews, 2000, 41(2): 147–162

    Article  Google Scholar 

  6. [6]

    Hruz P W, Mueckler M M. Structural analysis of the GLUT1 facilitative glucose transporter. Molecular Membrane Biology, 2001, 18(3): 183–193

    Article  Google Scholar 

  7. [7]

    Olson A L, Pessin J E. Structure, function, and regulation of the mammalian facilitative glucose transporter gene family. Annual Review of Nutrition, 1996, 16(1): 235–256

    Article  Google Scholar 

  8. [8]

    Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. The Journal of General Physiology, 1927, 8(6): 519–530

    Article  Google Scholar 

  9. [9]

    Cullinane C, Solomon B, Hicks R J. Imaging of molecular target modulation in oncology: challenges of early clinical trials. Clinical and Translational Imaging, 2014, 2(1): 5–12

    Article  Google Scholar 

  10. [10]

    Liu D Z, Sinchaikul S, Reddy P V G, et al. Synthesis of 2′-paclitaxel methyl 2-glucopyranosyl succinate for specific targeted delivery to cancer cells. Bioorganic & Medicinal Chemistry Letters, 2007, 17(3): 617–620

    Article  Google Scholar 

  11. [11]

    Airley R, Evans A, Mobasheri A, et al. Glucose transporter Glut-1 is detectable in peri-necrotic regions in many human tumor types but not normal tissues: Study using tissue microarrays. Annals of Anatomy, 2010, 192(3): 133–138

    Article  Google Scholar 

  12. [12]

    Jóźwiak P, Lipińska A. The role of glucose transporter 1 (GLUT1) in the diagnosis and therapy of tumors. Postępy Higieny i Medycyny Doświadczalnej, 2012, 66: 165–174 (in Polish)

    Google Scholar 

  13. [13]

    Ravi Kumar M N V. A review of chitin and chitosan applications. Reactive and Functional Polymers, 2000, 46(1): 1–27

    Article  Google Scholar 

  14. [14]

    Li J, Kong M, Cheng X J, et al. A facile method for preparing biodegradable chitosan derivatives with low grafting degree of poly(lactic acid). International Journal of Biological Macromolecules, 2011, 49(5): 1016–1021

    Article  Google Scholar 

  15. [15]

    Yang K, Gao T, Bao Z, et al. Preparation and characterization of a novel thermosensitive nanoparticle for drug delivery in combined hyperthermia and chemotherapy. Journal of Materials Chemistry B, 2013, 1(46): 6442–6448

    Article  Google Scholar 

  16. [16]

    Li P, Wang Y, Zeng F, et al. Synthesis and characterization of folate conjugated chitosan and cellular uptake of its nanoparticles in HT-29 cells. Carbohydrate Research, 2011, 346(6): 801–806

    Article  Google Scholar 

  17. [17]

    Chen X G, Li J, Cheng X J, et al. Process for preparing compounds of chitosan saccharified with aminosugar. US Patent, 8 202 971 B2, 2012-06-19

    Google Scholar 

  18. [18]

    Hansen M B, Nielsen S E, Berg K. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. Journal of Immunological Methods, 1989, 119(2): 203–210

    Article  Google Scholar 

  19. [19]

    Dong Y, Feng S S. Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. Biomaterials, 2004, 25(14): 2843–2849

    Article  Google Scholar 

  20. [20]

    Wang H, Zhao P, Su W, et al. PLGA/polymeric liposome for targeted drug and gene co-delivery. Biomaterials, 2010, 31(33): 8741–8748

    Article  Google Scholar 

  21. [21]

    Li J, Kong M, Cheng X J, et al. Preparation of biocompatible chitosan grafted poly(lactic acid) nanoparticles. International Journal of Biological Macromolecules, 2012, 51(3): 221–227

    Article  Google Scholar 

  22. [22]

    Danhier F, Feron O, Préat V. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anticancer drug delivery. Journal of Controlled Release, 2010, 148(2): 135–146

    Article  Google Scholar 

  23. [23]

    Yoo J W, Doshi N, Mitragotri S. Adaptive micro and nanoparticles: Temporal control over carrier properties to facilitate drug delivery. Advanced Drug Delivery Reviews, 2011, 63(14–15): 1247–1256

    Article  Google Scholar 

  24. [24]

    Hashida M, Takemura S, Nishikawa M, et al. Targeted delivery of plasmid DNA complexed with galactosylated poly(L-lysine). Journal of Controlled Release, 1998, 53(1–3): 301–310

    Article  Google Scholar 

  25. [25]

    Peer D, Karp J M, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2007, 2(12): 751–760

    Article  Google Scholar 

  26. [26]

    Choucair A, Soo P L, Eisenberg A. Active loading and tunable release of doxorubicin from block copolymer vesicles. Langmuir, 2005, 21(20): 9308–9313

    Article  Google Scholar 

  27. [27]

    Xun W, Wang H Y, Li Z Y, et al. Self-assembled micelles of novel graft amphiphilic copolymers for drug controlled release. Colloids and Surfaces B: Biointerfaces, 2011, 85(1): 86–91

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Jing Li or Xi-Guang Chen.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, J., Ma, FK., Dang, QF. et al. Glucose-conjugated chitosan nanoparticles for targeted drug delivery and their specific interaction with tumor cells. Front. Mater. Sci. 8, 363–372 (2014). https://doi.org/10.1007/s11706-014-0262-8

Download citation

Keywords

  • drug delivery
  • target
  • nanoparticle
  • glucose transporter (Glut)
  • chitosan (CS)