Skip to main content

Advertisement

SpringerLink
Log in

Peptide GE11–Polyethylene Glycol–Polyethylenimine for targeted gene delivery in laryngeal cancer

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The objective of this study was to evaluate the possibility of using GE11–polyethylene glycol–polyethylenimine (GE11-PEG-PEI) for targeted gene delivery to treat epidermal growth factor receptor (EGFR)-overexpressing laryngeal cancer. This study described the design, characterization, and in vitro and in vivo study of the nanocarrier GE11-PEG-PEI for gene delivery to treat laryngeal cancer. Analysis of the sizes and zeta potentials indicated that the formation of PEGylated complexes was dependent on the N/P ratio, and these complexes were capable of binding plasmid DNA and condensing DNA into small positively charged nanoparticles. The results also revealed that GE11-PEG-PEI had a weaker effect on cell survival in vitro. Gene transfection was performed on human laryngeal cancer Hep-2 cells in vitro and in vivo. Both the in vitro and in vivo results demonstrated that GE11-PEG-PEI had greater transfection efficiency than mPEG-PEI. Compared with mPEG-PEI/pORF-hTRAIL and saline, GE11-PEG-PEI/pORFh-TRAIL significantly (p < 0.05) reduced tumor growth in nude mice with laryngeal cancer. Moreover, the GE11-PEG-PEI/pORF-hTRAIL-treated groups showed more apoptosis than the mPEG-PEI/pORF-hTRAIL-treated groups. Therefore, our results showed that the peptide GE11 conjugated to PEG-PEI delivered significantly more genes to EGFR-overexpressing laryngeal cancer cells in vivo, indicating that GE11-PEG-PEI may be a suitable gene vector for treating EGFR-overexpressing laryngeal cancer.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kamimura K, Suda T, Zhang G, Liu D. Advances in gene delivery systems. Pharmaceut. Med. 2011;25(5):293–306.

    PubMed Central  PubMed  Google Scholar 

  2. Boussif O, Zanta MA, Behr JP. Optimized galenics improve in vitro gene transfer with cationic molecules up to 1000-fold. Gene Ther. 1996;3(12):1074–80.

    CAS  PubMed  Google Scholar 

  3. Sonawane ND, Szoka FC Jr, Verkman AS. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J Biol Chem. 2003;278(45):44826–31.

    Article  CAS  PubMed  Google Scholar 

  4. Lee M, Kim SW. Polyethylene glycol-conjugated copolymers for plasmid DNA delivery. Pharm Res. 2005;22(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  5. Bruzzese F, Leone A, Rocco M, Carbone C, Piro G, Caraglia M, Budillon A, et al. HDAC inhibitor vorinostat enhances the antitumor effect of gefitinib in squamous cell carcinoma of head and neck by modulating ErbB receptor expression and reverting EMT. J Cell Physiol. 2011;226(9):2378–90.

    Article  CAS  PubMed  Google Scholar 

  6. Wang JL, Tang GP, Shen J, Hu QL, Xu FJ, Wang QQ, et al. A gene nanocomplex conjugated with monoclonal antibodies for targeted therapy of hepatocellular carcinoma. Biomaterials. 2012;33(18):4597–607.

    Article  CAS  PubMed  Google Scholar 

  7. Li Z, Zhao R, Wu X, Sun Y, Yao M, Li J, et al. Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics. FASEB J. 2005;19(14):1978–85.

    Article  CAS  PubMed  Google Scholar 

  8. Milane L, Duan Z, Amiji M. Therapeutic efficacy and safety of paclitaxel/lonidamine loaded EGFR-targeted nanoparticles for the treatment of multi-drug resistant cancer. PLoS ONE. 2011;6(9):24075–86.

    Article  Google Scholar 

  9. Ren H, Gao C, Zhou L, Liu M, Xie C, Lu W. EGFR-targeted poly (ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization and in vitro evaluation. Drug Deliv. 2014;. doi:10.3109/10717544.2014.896057.

    Google Scholar 

  10. Wang J, Lei Y, Xie C, Lu W, Yan Z, Gao J, et al. Targeted gene delivery to glioblastoma using a C-end rule RGERPPR peptide-functionalised polyethylenimine complex. Int J Pharm. 2013;458(1):48–56.

    Article  CAS  PubMed  Google Scholar 

  11. Al-Dosari MS, Gao X. Nonviral gene delivery: principle, limitations, and recent progress. AAPS J. 2009;11(4):671–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Evans CH, Huard J. Gene therapy approaches to regenerating the musculoskeletal system. Nat Rev Rheumatol. 2015;11(4):234–42.

    Article  CAS  PubMed  Google Scholar 

  13. Nishikawa M, Hashida M. Nonviral approaches satisfying various requirements for effective in vivo gene therapy. Biol Pharm Bull. 2002;25(3):275–83.

    Article  CAS  PubMed  Google Scholar 

  14. Lei Y, Wang J, Xie C, Wagner E, Lu W, Li Y, et al. Glutathione-sensitive RGD-poly (ethylene glycol)-SS-polyethylenimine for intracranial glioblastoma targeted gene delivery. J Gene Med. 2013;15(8–9):291–305.

    CAS  PubMed  Google Scholar 

  15. Nguyen J, Xie X, Neu M, Dumitrascu R, Reul R, Sitterberg J, et al. Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs. J Gene Med. 2008;10(11):1236–46.

    Article  CAS  PubMed  Google Scholar 

  16. Petersen H, Fechner PM, Martin AL, Kunath K, Stolnik S, Roberts CJ, et al. Polyethylenimine-graft-poly (ethyleneglycol) copolymers: influence of copolymer block structure on DNA complex-ation and biological activities as gene delivery system. Bioconjug Chem. 2002;13(4):845–54.

    Article  CAS  PubMed  Google Scholar 

  17. Master A, Malamas A, Solanki R, Clausen DM, Eiseman JL, Sen Gupta A. A cell-targeted photodynamic nanomedicine strategy for head and neck cancers. Mol Pharm. 2013;10(5):1988–97.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Prabaharan M. Chitosan-based nanoparticles for tumor-targeted drug delivery. Int J Biol Macromol. 2015;72:1313–22.

    Article  CAS  PubMed  Google Scholar 

  19. Oh KS, Lee H, Kim JY, Koo EJ, Lee EH, Park JH, et al. The multilayer nanoparticles formed by layer by layer approach for cancer-targeting therapy. J Control Release. 2013;165(1):9–15.

    Article  CAS  PubMed  Google Scholar 

  20. Kwon IK, Lee SC, Han B, Park K. Analysis on the current status of targeted drug delivery to tumors. J Control Release. 2012;164(2):108–14.

    Article  CAS  PubMed  Google Scholar 

  21. Gratton SE, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ, Napier ME, et al. The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA. 2008;105(33):11613–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was financially supported by National Natural Science Foundation of China (No. 81001200) and School of Pharmacy, Fudan University & The Open Project Program of Key Lab of Smart Drug Delivery (Fudan University), Ministry of Education, China.

Conflict of interest

The authors declare no conflict of interest.

Ethical standard

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Author information

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Eye and ENT Hospital, Fudan University, 83 FenYang Road, Shanghai, 200031, China

    Henglei Ren, Liang Zhou & Chunli Gao

  2. Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, 201203, China

    Min Liu, Weiyue Lu & Chunli Gao

  3. Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China

    Min Liu & Weiyue Lu

Authors
  1. Henglei Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Weiyue Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chunli Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chunli Gao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ren, H., Zhou, L., Liu, M. et al. Peptide GE11–Polyethylene Glycol–Polyethylenimine for targeted gene delivery in laryngeal cancer. Med Oncol 32, 185 (2015). https://doi.org/10.1007/s12032-015-0624-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-015-0624-9

Keywords

Search

Navigation