Generation 4 polyamidoamine dendrimers is a novel candidate of nano-carrier for gene delivery agents in breast cancer treatment.
Polyamidoamine dendrimer (PAMAM-D) is a new gene vector developed in recent years. In this study, we successfully prepared G4PAMAM and detected its unique structure by NMR, FITR and TEM. We revealed that G4PAMAM could bind to human erythrocytes and BSA through electrostatic interaction respectively, and caused haemolysis and reduced bioavailability. However, G4PAMAM-VEGF-ASODN (antisense oligodeoxynucleotides) complex could prevent G4PAMAM from binding to the erythrocytes and BSA and remained stable as a conjugate, therefore the toxicity of the complex was reduced. Meanwhile, we showed that G4PAMAM could be used as a gene vector to deliver AODNs into breast cancer MDA-MB-231 cells without significant cell toxicity, and it enhanced cellular uptake of ODNs. In vivo experiment of human breast tumor xenograft mice model, G4PAMAM also showed more efficiency of accumulating VEGF-ASODN to inhibit the tumor vascularization of breast tumor tissue than naked AODN. Furthermore, G4PAMAM could protect DNA in cytoplasm from digestion of restriction enzymes, which was important to become an effective tool in gene research and therapy.
Wang
Pei
P
Department of Oncology, The First Hospital Affiliated to School of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
Zhao
Xin-Han
XH
Wang
Zhi-Yu
ZY
Meng
Min
M
Li
Xu
X
Ning
Qian
Q
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009757:Nylons / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D050091:Dendrimers; D009757:Nylons; C520550:PAMAM-G4; D042461:Vascular Endothelial Growth Factor A; D012710:Serum Albumin, Bovine