Journal of Materials Science: Materials in Medicine

, Volume 22, Issue 11, pp 2477–2485 | Cite as

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

  • Kai Zhu
  • Changfa Guo
  • Hao Lai
  • Wuli Yang
  • Yu Xia
  • Dong Zhao
  • Chunsheng Wang


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.


Vascular Endothelial Growth Factor Left Ventricular Ejection Fraction Reverse Transcription Polymerase Chain Reaction Transfection Efficiency Vascular Endothelial Growth Factor Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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).


  1. 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.CrossRefGoogle Scholar
  2. 2.
    Cristiano RJ. Viral and non-viral vectors for cancer gene therapy. Anticancer Res. 1998;18:3241–5.Google Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 5.
    Tomalia DA, Fréchet JMJ. Discovery of dendrimers and dendritic polymers: a brief historical perspective. J Polym Sci A. 2002;40:2719–28.CrossRefGoogle Scholar
  6. 6.
    Gao C, Yan D. Hyperbranched polymers: from synthesis to applications. Prog Polym Sci. 2004;29:183–275.CrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.Google Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.Google Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 17.
    Dennig J, Duncan E. Gene transfer into eukaryotic cells using activated polyamidoamine dendrimers. J Biotechnol. 2002;90:339–47.Google Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.Google Scholar
  20. 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.Google Scholar
  21. 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.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Cardiac Surgery, Zhongshan HospitalFudan University & Shanghai Institute of Cardiovascular DiseasesShanghaiPeople’s Republic of China
  2. 2.Key Laboratory of Molecular Engineering of Polymers (Ministry of Education), Department of Macromolecular ScienceFudan UniversityShanghaiPeople’s Republic of China

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