Synthesis and evaluation of a glutamic acid-modified hPAMAM complex as a promising versatile gene carrier.
Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM-Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2 h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM-Glu20 represented much higher (p < 0.05) than that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells. Cellular uptake of the hPAMAM-Glu20 in MDA-MB231 cells, 173.56 ± 1.37%, was significantly higher than that of MCF7 cells, 65.00 ± 1.73% (p < 0.05). The results indicated that hPAMAM-Glu20-mediated gene delivery to breast cancer cells is a feasible and effective strategy that may provide a new therapeutic avenue as a non-viral gene delivery carrier. In addition, it was found that hPAMAM-glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.
a Medical Physics and Biomedical Engineering and Nanomedicine Department, Faculty of Medicine, Shahid Beheshti Medical University , Tehran , Iran .
Mohammad
M
Hemmati
b Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences , Tehran , Iran .
Bahram
B
Kazemi
c Institute for Color Science and Technology (ICST), the Ministry of Science, Research and Technology , Tehran , Iran , and.
Farhood
F
Najafi
a Medical Physics and Biomedical Engineering and Nanomedicine Department, Faculty of Medicine, Shahid Beheshti Medical University , Tehran , Iran .
Amir
A
Zarebkohan
d Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences , Tehran , Iran.
Reza
R
Shirkoohi
D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D018698:Glutamic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage; D061986:MCF-7 Cells; D011073:Polyamines / Q000008:administration & dosage* / Q000737:chemistry*; D014162:Transfection / Q000379:methods
D050091:Dendrimers; D008055:Lipids; C086724:Lipofectamine; C531249:Poly(amidoamine); D011073:Polyamines; D018698:Glutamic Acid; D004247:DNA
Breast cancer; gene delivery; glutamic acid; hPAMAM; hPAMAM–Glu; sFlt-1