title: Synthesis of a novel PEGDGA-coated hPAMAM complex as an efficient and biocompatible gene delivery vector: an in vitro and in vivo study.
abstract: hPAMAM/DNA polyplexes, compared to viral vectors, display unique characteristics including more safety, less immune response outcomes, a simpler synthesis and an easier process. Given the importance of these polymers, hPAMAM coated with the PEGDGA copolymer was developed as a promising non-viral gene carrier. In the present study, a new complex of hPAMAM, PEGDGA-modified hyperbranched polyamidoamine (hPAMAM), was established as a versatile non-viral gene vector. The hPAMAM polymer was synthesized by using a modified one-pot method. The resulting hPAMAM-PEGDGA polymer was able to efficiently protect encapsulated-DNA against degradation for over 2 h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM-PEGDGA represented much higher (p < 0.05) than that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells (an approximately 4.5-fold increase). Cellular uptake of hPAMAM-PEGDGA in MDA-MB231 cells, 254.79 ± 2.1, was significantly higher than that in MCF7 cells, 51.61 ± 6.1 (p < 0.05). EMA-labeled DNA can be clearly observed in the tumor tissue of mice receiving hPAMAM-PEGDGA/EMA-labeled DNA. However, a significant number of fluorescent spots can be found in the tumor tissue of mice receiving hPAMAM/DNA, when compared to those treated with naked hPAMAM/DNA. It has been observed that GFP is expressed more highly in hPAMAM-PEGDGA/EMA-labeled/DNA than the one in PAMAM/DNA. The results indicated that hPAMAM-PEGDGA-mediated gene delivery to breast cancer cells is a feasible and effective strategy that may offer a new therapeutic avenue as a non-viral gene delivery carrier. Notably, According to these findings, this newly-introduced copolymer, the hPAMAM-PEGDGA complex, has proved to be a promising strategy for drug or gene delivery to tissues or cell types of interest, particularly to triple-negative breast cancer.
authors: a Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors: Mohammad
authors: M
authors: Hemmati
authors: b Department of Resin and Additives , Institute for Color Science and Technology , Tehran , Iran.
authors: Farhood
authors: F
authors: Najafi
authors: c Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences , Tehran , Iran.
authors: Reza
authors: R
authors: Shirkoohi
authors: d School of Pharmacy, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors: Hamid Reza
authors: HR
authors: Moghimi
authors: a Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors: Amir
authors: A
authors: Zarebkohan
authors: e Department of Biotechnology , Faculty of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences , Tehran , Iran , and.|f Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors: Bahram
authors: B
authors: Kazemi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D008055:Lipids; C086724:Lipofectamine; C104700:PAMAM Starburst; D011108:Polymers; D018698:Glutamic Acid; D011092:Polyethylene Glycols; D004247:DNA; C000595213:polyethylene glycol 400
keywords: Breast cancer; copolymer PEG–glutamic acid; gene delivery; glutamic acid; hPAMAM; hPAMAM–Glu