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Dendrimer-Modified Magnetic Nanoparticles Enhance Efficiency of Gene Delivery System

¹ Department of Bio-Nano-Science and Engineering, National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University; ² Breast Cancer Therapy Center of Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China; and ³ Department of Mechanical Engineering, University of California at Riverside, Riverside, California

Requests for reprints: Daxiang Cui, Department of Bio-Nano-Science and Engineering, National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, People's Republic of China. Phone: 86-21-62933291; Fax: 86-21-62933291; E-mail: dxcui{at}sjtu.edu.cn.

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. [Cancer Res 2007;67(17):8156–63]