Skip to main content

Advertisement

Log in

Preparation of EGFR monoclonal antibody conjugated nanoparticles and targeting to hepatocellular carcinoma

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

This study aims to determine the sensitivity, specificity and accuracy of epidermal growth factor receptor monoclonal antibody (EGFRmAb) modified poly(lactic acid-co-l-lysine) nanoparticles (PLA-PLL-EGFRmAb) NPs delivery system to EGFR positive cancer cells. In the study, a new PLA-PLL-EGFRmAb NPs was prepared. The cellular cytotoxicity, cellular uptake, and the targeted effect for hepatocellular carcinoma of PLA-PLL-EGFRmAb NPs were investigated. In vitro, the findings of Flow cytometry and Confocal Laser scanning Biological Microscopy showed that PLA-PLL-EGFRmAb NPs can bind to hepatocellular carcinoma cells and were uptaken effectively. In vivo in the SMMC-7721 xenograft mouse model, PLA-PLL-EGFRmAb NPs could target to the tumor effectively, which demonstrated a better targeting. These results showed that the PLA-PLL-EGFRmAb NPs have the potential to be used as a target delivery carrier for tumor therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Wolinsky JB, Grinstaff MW. Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv Drug Deliv Rev. 2008;60:1037–55.

    Article  CAS  PubMed  Google Scholar 

  2. Vasir JK, Labhasetwar V. Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev. 2007;59:718–28.

    Article  CAS  PubMed  Google Scholar 

  3. Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86:215–23.

    Article  CAS  PubMed  Google Scholar 

  4. Haley B, Frenkel E. Nanoparticles for drug delivery in cancer treatment. Urol Oncol. 2008;26:57–64.

    CAS  PubMed  Google Scholar 

  5. Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303:1818–22.

    Article  CAS  PubMed  ADS  Google Scholar 

  6. Stayton PS, Hoffman AS, Murthy N, Lackey C, Cheung C, Tan P, et al. Molecular engineering of proteins and polymers for targeting and intracellular delivery of therapeutics. J Control Release. 2000;65:203–20.

    Article  CAS  PubMed  Google Scholar 

  7. Wartlick H, Michaelis K, Balthasar S, Strebhardt K, Kreuter J, Langer K. Highly specific HER2-mediated cellular uptake of antibody-modified nanoparticles in tumour cells. J Drug Target. 2004;12:461–71.

    Article  CAS  PubMed  Google Scholar 

  8. Anhorn MG, Wagner S, Kreuter J, Langer K, von Briesen H. Specific targeting of HER2 overexpressing breast cancer cells with doxorubicin-loaded trastuzumab-modified human serum albumin nanoparticles. Bioconjug Chem. 2008;19:2321–31.

    Article  CAS  PubMed  Google Scholar 

  9. Mitra A, Coleman T, Borgman M, Nan A, Ghandehari H, Line BR. Polymeric conjugates of mono- and bi-cyclic alphavbeta3 binding peptides for tumor targeting. J Control Release. 2006;114:175–83.

    Article  CAS  PubMed  Google Scholar 

  10. Xiong XB, Huang Y, Lu WL, Zhang X, Zhang H, Nagai T, et al. Enhanced intracellular delivery and improved antitumor efficacy of doxorubicin by sterically stabilized liposomes modified with a synthetic RGD mimetic. J Control Release. 2005;107:262−75.

    Article  CAS  PubMed  Google Scholar 

  11. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.

    Article  CAS  PubMed  Google Scholar 

  12. Hirsch FR, Scagliotti GV, Langer CJ, Varella-Garcia M, Franklin WA. Epidermal growth factor family of receptors in preneoplasia and lung cancer. Perspectives for targeted therapies. Lung Cancer. 2003;41(suppl 1):S29–42.

    Article  PubMed  Google Scholar 

  13. Maihle NJ, Baron AT, Barrette BA, Boardman CH, Christensen TA, Cora EW, et al. EGF/ErbB receptor family in ovarian cancer. Cancer Treat Res. 2002;107:247–58.

    CAS  PubMed  Google Scholar 

  14. Di-Lorenzo G, Bianco R, Tortora G, Ciardiello F. Involvement of growth factor receptors of the epidermal growth factor receptor family in prostate cancer development and progression to androgen independence. Clin Prostate Cancer. 2003;2:50−7.

    CAS  Google Scholar 

  15. Meert AP, Verdebout JM, Martin B, Ninane V, Feoli F, Sculier JP. Epidermal growth factor receptor expression in pre-invasive and early invasive bronchial lesions. Eur Respir J. 2003;21:611–5.

    Article  CAS  PubMed  Google Scholar 

  16. Piyathilake CJ, Frost AR, Manne U, Weiss H, Bell WC, Heimburger D, et al. Differential expression of growth factors in squamous cell carcinoma and precancerous lesions of the lung. Clin Cancer Res. 2002;8:734–44.

    CAS  PubMed  Google Scholar 

  17. Selvaggi G, Novello S, Torri V, Leonardo E, De Giuli P, Borasio P, et al. Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer. Ann Oncol. 2004;15:28–32.

    Article  CAS  PubMed  Google Scholar 

  18. Sorkin A. Internalization of the epidermal growth factor receptor: role in signalling. Biochem Soc Trans. 2001;29:480–4.

    Article  CAS  PubMed  Google Scholar 

  19. Zhou Y, Drummond DC, Zou H, Hayes ME, Adams GP, Kirpotin DB, et al. Impact of singlechain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptorexpressing tumor cells. J Mol Biol. 2007;371:934–47.

    Article  CAS  PubMed  Google Scholar 

  20. Gao HP, Jiang H, Wang HM, Li ZH. Preparation and identification of anti-EGFRvIII/EGFR monoclonal antibody 9B9. Chin J Cancer Biother. 2009;16:391−5.

    Google Scholar 

  21. Yu H, Guo XJ, Qi XL, Liu PF, Shen XY, Duan YR. Synthesis and characterization of arginine-glycine-aspartic peptides conjugated poly (lactic acid-co-l-lysine) diblock copolymer. J Mater Sci Mater Med. 2008;19:1275–81.

    Article  CAS  PubMed  Google Scholar 

  22. Duan YR, Xu S, Wang Q, Liu J, Zhang ZR. Optimization of preparation of DHAQ-loaded PEG-PLGA-PEG nanoparticles using central composite design. J Mater Sci Mater Med. 2006;17:559–63.

    Article  CAS  PubMed  Google Scholar 

  23. Eliyahu H, Barenholz Y, Domb AJ. Polymers for DNA delivery. Molecules. 2005;10:34–64.

    Article  CAS  PubMed  Google Scholar 

  24. Veiseh O, Kievit FM, Gunn JW, Ratner BD, Zhang M. A ligand-mediated nanovector for targeted gene delivery and transfection in cancer cells. Biomaterials. 2009;30:649–57.

    Article  CAS  PubMed  Google Scholar 

  25. Yoshizawa T, Hattori Y, Hakoshima M, Koga K, Maitani Y. Folate-linked lipid-based nanoparticles for synthetic siRNA delivery in KB tumor xenografts. Eur J Pharm Biopharm. 2008;70:718–25.

    Article  CAS  PubMed  Google Scholar 

  26. Pan J, Feng SS. Targeting and imaging cancer cells by folate decorated, “quantum dots loaded nanoparticles of biodegradable polymers”. Biomaterials. 2009;30:1176–83.

    Article  CAS  PubMed  Google Scholar 

  27. Chatterjee DK, Fong LS, Zhang Y. Nanoparticles in photodynamic therapy: an emerging paradigm. Adv Drug Deliv Rev. 2008;60:1627–37.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by National 973 Basic Research Program of China (No. 20108529902), National 863 Research Program of China (No. 2007AA021203), National Natural Science Foundation of China (No. 50673058), Shanghai Municipal Public Health Bureau (No. 2008Y088) and Nano-Science and Technology from Science and Technology Commission of Shanghai Municipality (No. 0852nm05800).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hongzhi Wang or Yourong Duan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, P., Li, Z., Zhu, M. et al. Preparation of EGFR monoclonal antibody conjugated nanoparticles and targeting to hepatocellular carcinoma. J Mater Sci: Mater Med 21, 551–556 (2010). https://doi.org/10.1007/s10856-009-3925-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-009-3925-8

Keywords

Navigation