Methotrexate-Coated Complexes of Plasmid DNA and Polyethylenimine for Gene Delivery

• Kodama Yukinobu

  Department of Hospital Pharmacy, Nagasaki University Hospital

• Noda Ryo

  Department of Hospital Pharmacy, Nagasaki University Hospital

• Sato Kayoko

  Department of Hospital Pharmacy, Nagasaki University Hospital

• Harasawa Hitomi

  Department of Hospital Pharmacy, Nagasaki University Hospital

• Kurosaki Tomoaki

  Department of Hospital Pharmacy, Nagasaki University Hospital

• Nakagawa Hiroo

  Department of Hospital Pharmacy, Nagasaki University Hospital

• Nakamura Tadahiro

  Department of Hospital Pharmacy, Nagasaki University Hospital

• Kitahara Takashi

  Department of Hospital Pharmacy, Nagasaki University Hospital

• Muro Takahiro

  Department of Hospital Pharmacy, Nagasaki University Hospital

• Sasaki Hitoshi

  Department of Hospital Pharmacy, Nagasaki University Hospital

Abstract

Folate receptors are overexpressed on the surface cancer cells. We successfully constructed a new gene delivery vector of methotrexate (MTX)-coated plasmid DNA–polyethylenimine (pDNA–PEI) complexes (PEI complexes) by electrostatic binding. The stable anionic nanoparticle was optimized at MTX charge ratios of 120 or more. pDNA–PEI–MTX complexes (MTX complexes) demonstrated gene expression efficiency as high as cationic pDNA–PEI complexes in the mouse melanoma cell line, B16-F10. The MTX complexes were taken up by the cell-specific uptake mechanisms via the folate receptor. MTX-coated complexes are useful as endocytosis ligands. The MTX120 complexes exhibited no blood aggregation. The transgene efficiency of MTX120 complexes in the liver and spleen after their intravenous administration was higher than that of PEI complexes. Therefore, MTX complexes are expected as a new gene vector in the future.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 41 (10), 1537-1542, 2018-10-01

  The Pharmaceutical Society of Japan

Keywords

• methotrexate
• gene delivery
• ternary complex
• DNA

Details

• CRID: 1390845713002935552
• NII Article ID: 130007494219
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b18-00144
• ISSN: 13475215
• ISSN: 09186158
• HANDLE: 10069/38631
• NDL BIB ID: 029238526
• PubMed: 30270323
• Web Site: https://nagasaki-u.repo.nii.ac.jp/records/1368
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I029238526
• Web Site: https://www.jstage.jst.go.jp/article/bpb/41/10/41_b18-00144/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2019149467
• Text Lang: en
• Data Source:
  • JaLC
  • IRDB
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed