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Pharmaceutical Research

, Volume 25, Issue 12, pp 2924–2936 | Cite as

Polyplex Micelles from Triblock Copolymers Composed of Tandemly Aligned Segments with Biocompatible, Endosomal Escaping, and DNA-Condensing Functions for Systemic Gene Delivery to Pancreatic Tumor Tissue

  • Kanjiro Miyata
  • Makoto Oba
  • Mitsunobu R. Kano
  • Shigeto Fukushima
  • Yelena Vachutinsky
  • Muri Han
  • Hiroyuki Koyama
  • Kohei Miyazono
  • Nobuhiro Nishiyama
  • Kazunori KataokaEmail author
Research Paper

Abstract

Purpose

For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine).

Materials and Methods

The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues.

Results

The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-β type I receptor (TβR-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts.

Conclusion

The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.

KEY WORDS

gene delivery PEG polyplex micelle TGF-β inhibitor triblock copolymer 

Notes

ACKNOWLEDGEMENTS

This work was financially supported by the Core Research Program for Evolutional Science and Technology (CREST) from the Japan Science and Technology Corporation (JST) as well as by Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Kanjiro Miyata
    • 1
    • 6
  • Makoto Oba
    • 2
  • Mitsunobu R. Kano
    • 3
    • 6
  • Shigeto Fukushima
    • 4
  • Yelena Vachutinsky
    • 1
  • Muri Han
    • 5
  • Hiroyuki Koyama
    • 2
  • Kohei Miyazono
    • 3
    • 6
  • Nobuhiro Nishiyama
    • 4
    • 6
  • Kazunori Kataoka
    • 1
    • 4
    • 5
    • 6
    Email author
  1. 1.Department of Bioengineering, Graduate School of EngineeringThe University of TokyoTokyoJapan
  2. 2.Department of Clinical Vascular Regeneration, Graduate School of MedicineThe University of TokyoTokyoJapan
  3. 3.Department of Molecular Pathology, Graduate School of MedicineThe University of TokyoTokyoJapan
  4. 4.The Center for Disease Biology and Integrative Medicine, Graduate School of MedicineThe University of TokyoTokyoJapan
  5. 5.Department of Materials EngineeringGraduate School of EngineeringTokyoJapan
  6. 6.Center for NanoBio IntegrationThe University of TokyoTokyoJapan

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