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A novel magnetic crystal–lipid nanostructure for magnetically guided in vivo gene delivery

Nature Nanotechnology volume 4, pages 598–606 (2009)Cite this article

Abstract

Cancer gene therapy requires a safe and effective gene delivery system. Polymer- and lipid-coated magnetic nanocrystals have been used to deliver silencing RNA, but synthesizing these magnetic vectors is difficult. Here, we show that a new nanoparticle formulation can be magnetically guided to deliver and silence genes in cells and tumours in mice. This formulation, termed LipoMag, consists of an oleic acid-coated magnetic nanocrystal core and a cationic lipid shell. When compared with the commercially available PolyMag formulation, LipoMag displayed more efficient gene silencing in 9 of 13 cell lines, and better anti-tumour effects when systemically administered to mice bearing gastric tumours. By delivering an optimized sequence of a silencing RNA that targets the epidermal growth factor receptor of tumour vessels, the intended therapeutic benefit was achieved with no evident adverse immune reaction or untoward side effects.

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Figure 1: The preparation and in vitro nucleic acid delivery efficiency of LipoMag.
Figure 2: LipoMag-mediated delivery of nucleic acid to tumour lesions under a magnetic field.
Figure 3: Biodistribution of siRNA delivered by LipoMag and PolyMag.
Figure 4: Screening EGFR-targeted siRNA and avoiding cytokine induction by chemical modification.
Figure 5: Anti-tumour effect of tumour vessel-targeted RNA interference delivered by LipoMag and PolyMag.
Figure 6: RACE-PCR analysis.

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Acknowledgements

We dedicate this study to the late T. Terada for his fight against cancer, which came too early in his life. HSC39, HSC43 and HSC45 were kindly donated by K. Yanagihara. OCUM-2MD3 was kindly donated by M. Yashiro. This work was supported by an Industrial Technology Research Grant, Program 08C46049a (2008), from the New Energy and Industrial Technology Development Organization (NEDO) of Japan, the Futaba Electronics Memorial Foundation (2008), the Takeda Science Foundation (2007) and the Tsuchiya Foundation (2006).

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Authors and Affiliations

  1. Institute of Clinical Medicine and Research, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, 277-8567, Japan

    Yoshihisa Namiki, Yukiko Ishii, Akihito Tsubota, Yasuo Mabashi, Yoko Yumoto, Sadayori Hoshina, Kiyotaka Fujise & Norio Tada

  2. Department of Radiology, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, 277-8567, Japan

    Tamami Namiki & Yukiko Ishii

  3. Department of Laboratory Medicine, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, 277-8567, Japan

    Hiroshi Yoshida

  4. Division of Gastroenterology and Hepatology, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, 277-8567, Japan

    Shigeo Koido, Makoto Mitsunaga & Kiyotaka Fujise

  5. Laboratory Animal Facilities, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, 277-8567, Japan

    Kouichi Nariai

  6. Department of Surgery, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, 277-8567, Japan

    Satoru Yanagisawa & Hideyuki Kashiwagi

  7. Division of General Medicine, The Jikei University School of Medicine, 163-1 Kashiwa-shita, Kashiwa, Chiba, 277-8567, Japan

    Norio Tada

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  1. Yoshihisa Namiki
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Contributions

Y.N. and T.N. conceived and designed the experiments. Y.N., H.Y., A.T., K.N., S.K, M.M., Y.M. and Y.Y. performed the experiments. Y.N., H.Y. and Y.I. co-wrote the paper. T.N. performed the statistical analysis. S.Y. and H.K. supplied the clinical specimens from gastric cancer patients. S.H., K.F. and N.T. supervised the project.

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Correspondence to Yoshihisa Namiki.

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Namiki, Y., Namiki, T., Yoshida, H. et al. A novel magnetic crystal–lipid nanostructure for magnetically guided in vivo gene delivery. Nature Nanotech 4, 598–606 (2009). https://doi.org/10.1038/nnano.2009.202

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