Dendrimer-modified magnetic nanoparticles enhance efficiency of gene delivery system.
Magnetic nanoparticles (MNP) with a diameter of 8 nm were modified with different generations of polyamidoamine (PAMAM) dendrimers and mixed with antisense survivin oligodeoxynucleotide (asODN). The MNP then formed asODN-dendrimer-MNP composites, which we incubated with human tumor cell lines such as human breast cancer MCF-7, MDA-MB-435, and liver cancer HepG2 and then analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, quantitative reverse transcription-PCR, Western blotting, laser confocal microscopy, and high-resolution transmission electron microscopy. Results showed that the asODN-dendrimer-MNP composites were successfully synthesized, can enter into tumor cells within 15 min, caused marked down-regulation of the survivin gene and protein, and inhibited cell growth in dose- and time-dependent means. No.5 generation of asODN-dendrimer-MNP composites exhibits the highest efficiency for cellular transfection and inhibition. These results show that PAMAM dendrimer-modified MNPs may be a good gene delivery system and have potential applications in cancer therapy and molecular imaging diagnosis.
Pan
Bifeng
B
Department of Bio-Nano-Science and Engineering, National Key Laboratory of Nano/Micro Fabrication Technology, Shanghai Jiao Tong University, Shanghai, PR China.
Cui
Daxiang
D
Sheng
Yuan
Y
Ozkan
Cengiz
C
Gao
Feng
F
He
Rong
R
Li
Qing
Q
Xu
Ping
P
Huang
Tuo
T
D049109:Cell Proliferation; D002470:Cell Survival; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D018922:HL-60 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008280:Magnetics; D053768:Metal Nanoparticles / Q000627:therapeutic use*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000628:therapy*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D000077022:Survivin; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured