Skip to main content
SpringerLink
Log in

Novel hyperbranched polyamidoamine nanoparticles for transfecting skeletal myoblasts with vascular endothelial growth factor gene for cardiac repair

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

Abstract

We investigated the feasibility and efficacy of hyperbranched polyamidoamine (hPAMAM) mediated human vascular endothelial growth factor-165 (hVEGF165) gene transfer into skeletal myoblasts for cardiac repair. The hPAMAM was synthesized using a modified one-pot method. Encapsulated DNA was protected by hPAMAM from degradation for over 120 min. The transfection efficiency of hPAMAM in myoblasts was 82.6 ± 7.0% with cell viability of 94.6 ± 1.4% under optimal conditions. The hPAMAM showed much higher transfection efficiency (P < 0.05) than polyetherimide and Lipofectamine 2000 with low cytotoxicity. The transfected skeletal myoblasts gave stable hVEGF165 expression for 18 days. After transplantation of hPAMAM–hVEGF165 transfected cells, apoptotic myocardial cells decreased at day 1 and heart function improved at day 28, with increased neovascularization (P < 0.05). These results indicate that hPAMAM-based gene delivery into myoblasts is feasible and effective and may serve as a novel and promising non-viral DNA vehicle for gene therapy in myocardial infarction.

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
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Haider HKh, Ye L, Jiang S, Ge R, Law PK, Chua T, et al. Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor. J Mol Med. 2004;82:539–49.

    Article  Google Scholar 

  2. Cristiano RJ. Viral and non-viral vectors for cancer gene therapy. Anticancer Res. 1998;18:3241–5.

    CAS  Google Scholar 

  3. Zhang Y, Liu JY, Yang F, Zhang YJ, Yao Q, Cui TY, et al. A new strategy for assembling multifunctional nanocomposites with iron oxide and amino-terminated PAMAM dendrimers. J Mater Sci: Mater Med. 2009;20:2433–40.

    Article  CAS  Google Scholar 

  4. Eichman JD, Bielinska AU, Kukowska-Latallo JF, Baker JR Jr. The use of PAMAM dendrimers in the efficient transfer of genetic material into cells. Pharm Sci Technol Today. 2000;3:232–45.

    Article  CAS  Google Scholar 

  5. Tomalia DA, Fréchet JMJ. Discovery of dendrimers and dendritic polymers: a brief historical perspective. J Polym Sci A. 2002;40:2719–28.

    Article  CAS  Google Scholar 

  6. Gao C, Yan D. Hyperbranched polymers: from synthesis to applications. Prog Polym Sci. 2004;29:183–275.

    Article  CAS  Google Scholar 

  7. Cao L, Yang WL, Wang CC, Fu SK. Synthesis and striking fluorescence properties of hyperbranched poly(amido amine). J Macromol Sci A. 2007;44:417–24.

    Article  CAS  Google Scholar 

  8. Tomalia DA, Naylor AM, Goddard WA. Starburst dendrimers: molecular-level control of size, shape, surface chemistry, topology, and flexibility from atoms to macroscopic matter. Angew Chem Int Ed. 1990;29:138–75.

    Article  Google Scholar 

  9. Koh GY, Kim SJ, Klug MG, Park K, Soonpaa MH, Field LJ. Targeted expression of transforming growth factor-beta 1 in intracardiac grafts promotes vascular endothelial cell DNA synthesis. J Clin Invest. 1995;95:114–21.

    Article  CAS  Google Scholar 

  10. Suzuki K, Brand NJ, Smolenski RT, Jayakumar J, Murtuza B, Yacoub MH. Development of a novel method for cell transplantation through the coronary artery. Circulation. 2000;102(19 Suppl 3):III359–64.

    CAS  Google Scholar 

  11. Ahn YH, Bensadoun JC, Aebischer P, Zurn AD, Seiger A, Björklund A, et al. Increased fiber outgrowth from xeno-transplanted human embryonic dopaminergic neurons with co-implants of polymer-encapsulated genetically modified cells releasing glial cell line-derived neurotrophic factor. Brain Res Bull. 2005;66:135–42.

    Article  CAS  Google Scholar 

  12. Akiyama H,  Ito A, Kawabe Y, Kamihira M. Genetically engineered angiogenic cell sheets using magnetic force-based gene delivery and tissue fabrication techniques. Biomaterials. 2010;31:1251–9.

    Article  CAS  Google Scholar 

  13. Ye L, Haider HKh, Tan R, Toh W, Law PK, Tan W, et al. Transplantation of nanoparticle transfected skeletal myoblasts overexpressing vascular endothelial growth factor-165 for cardiac repair. Circulation. 2007;116(Suppl I):I113–20.

    CAS  Google Scholar 

  14. Kim TI, Seo HJ, Choi JS, Jang HS, Baek JU, Kim K, et al. PAMAM-PEG-PAMAM: novel triblock copolymer as a biocompatible and efficient gene delivery carrier. Biomacromolecules. 2004;5:2487–92.

    Article  CAS  Google Scholar 

  15. Gu SZ, Zhao XH, Zhang LX, Li L, Wang ZY, Meng M, et al. Anti-angiogenesis effect of generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide on breast cancer in vitro. J Zhejiang Univ Sci B. 2009;10:159–67.

    Article  CAS  Google Scholar 

  16. Intra J, Salem AK. Fabrication, characterization and in vitro evaluation of poly (d,l-lactide-co-glycolide) microparticles loaded with polyamidoamine-plasmid DNA dendriplexes for applications in nonviral gene delivery. J Pharm Sci. 2010;99:368–84.

    Article  CAS  Google Scholar 

  17. Dennig J, Duncan E. Gene transfer into eukaryotic cells using activated polyamidoamine dendrimers. J Biotechnol. 2002;90:339–47.

    CAS  Google Scholar 

  18. Yu JH, Quan JS, Huang J, Nah JW, Cho CS. Degradable poly(amino ester) based on poly(ethylene glycol) dimethacrylate and polyethylenimine as a gene carrier: molecular weight of PEI affects transfection efficiency. J Mater Sci: Mater Med. 2009;20:2501–10.

    Article  CAS  Google Scholar 

  19. Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM. VEGF gene delivery to myocardium: deleterious effects of unregulated expression. Circulation. 2000;102:898–901.

    CAS  Google Scholar 

  20. Suzuki K, Murtuza B, Smolenski RT, Sammut IA, Suzuki N, Kaneda Y, et al. Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor-expressing skeletal myoblasts. Circulation. 2001;104(12 Suppl 1):I207–12.

    CAS  Google Scholar 

  21. Hoffmann J, Glassford AJ, Doyle TC, Robbins RC, Schrepfer S, Pelletier MP. Angiogenic effects despite limited cell survival of bone marrow-derived mesenchymal stem cells under ischemia. Thorac Cardiovasc Surg. 2010;58:136–42.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful for the support of Shanghai Pujiang Program (Grant No. 10PJ1402000), the Doctor Project for Young Teachers of Ministry of Education (Grant No. 20090071120032), and the National Science Foundation of China (Grant No. 20874015).

Author information

Authors and Affiliations

  1. Department of Cardiac Surgery, Zhongshan Hospital, Fudan University & Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, People’s Republic of China

    Kai Zhu, Changfa Guo, Hao Lai, Yu Xia, Dong Zhao & Chunsheng Wang

  2. Key Laboratory of Molecular Engineering of Polymers (Ministry of Education), Department of Macromolecular Science, Fudan University, Shanghai, 200433, People’s Republic of China

    Wuli Yang

Authors
  1. Kai Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Changfa Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hao Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wuli Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yu Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chunsheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Changfa Guo or Chunsheng Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, K., Guo, C., Lai, H. et al. Novel hyperbranched polyamidoamine nanoparticles for transfecting skeletal myoblasts with vascular endothelial growth factor gene for cardiac repair. J Mater Sci: Mater Med 22, 2477–2485 (2011). https://doi.org/10.1007/s10856-011-4424-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-011-4424-2

Keywords

Search

Navigation