Transfection study using multicellular tumor spheroids for screening non-viral polymeric gene vectors with low cytotoxicity and high transfection efficiencies

Muri Han, Younsoo Bae, Nobuhiro Nishiyama, Kanjiro Miyata, Makoto Oba, Kazunori Kataoka

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Polyplexes consisting of plasmid DNA and polycations have received much attention as promising vectors for gene transfer. For effective gene therapy, polycations with different polyamine structures in the side chain were developed to ensure their buffering capacity for endosomal escape, and their PEGylated block copolymers were developed to increase their stability and biocompatibility. The effects of the chemical structures of polycations and their PEGylation on transfection and cytotoxicity were elucidated by use of a three-dimensional multicellular tumor spheroid of human hepatoma HuH-7 cells. Various features of transfection with polyplex micelles, which have been hard to observe in conventional monolayer cultures, were revealed by the multicellular tumor spheroid (MCTS) model in terms of cytotoxicity and time-dependent behaviors of transfected gene expression under three-dimensional microenvironments. By using this system, the polyplex micelle from poly(ethylene glycol)-b-poly(N-substituted asparagine) copolymers having the N-(2-aminoethyl)-2-aminoethyl group in the side chain (PEG-b-P[Asp(DET)] polyplex micelle) was proved to achieve high transfection efficiencies as well as low cytotoxicity, both of which are critical properties for successful in vivo gene delivery.

Original languageEnglish
Pages (from-to)38-48
Number of pages11
JournalJournal of Controlled Release
Volume121
Issue number1-2
DOIs
StatePublished - Aug 16 2007

Bibliographical note

Funding Information:
We are grateful to Mr. S. Fukushima and Mr. S. Asano for polymer synthesis. This work was supported by the Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), and the Health and Labor Sciences Research Grants in Research on Advanced Medical Technology in Nanomedicine Area from the Ministry of Health, Labor and Welfare (MHLW), Japan.

Keywords

  • Block copolymer
  • Non-viral gene vector
  • Polyplex micelle
  • Spheroid

ASJC Scopus subject areas

  • Pharmaceutical Science

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