A DNA microarray-based analysis of immune-stimulatory and transcriptional responses of dendritic cells to KALA-modified nanoparticles

Hidetaka Akita, Soichiro Ishii, Naoya Miura, Sharif Mohammad Shaheen, Yasuhiro Hayashi, Takashi Nakamura, Noritada Kaji, Yoshinobu Baba, Hideyoshi Harashima

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Technologies for the transfection of antigen-encoding genes into the dendritic cells, and subsequent immune-activation are both prerequisites for a successful DNA vaccine. We herein report on the density-dependent enhancement of transgene expression by the simple modification by stearyl-conjugated KALA, an α-helical peptide (STR-KALA), onto a lipid envelope-type nanoparticle (the R8-MEND, an octaarginine-modified multifunctional envelope-type nano device). The enhanced transgene expression in the KALA-modified R8-MEND (R8/KALA-MEND) cannot be explained by cellular uptake and nuclear delivery efficacy. Thus, the post-nuclear delivery process (i.e. transcription), but not intracellular trafficking processes attributed the enhanced transfection efficacy. Microarray analyses revealed that transfection with the R8/KALA-MEND resulted in a greater perturbation in host genes expression in comparison with the R8-MEND and that this effect was time-dependent. Further pathway analyses in the category of transcription-related genes and a gene ontology analysis indicated that the R8/KALA-MEND stimulated the expression of transcription factors that are closely related to immune-activation (i.e. NF- kB and STAT). Inhibition of the transfection efficacy by blockage of the STAT pathways revealed that the enhanced transcription activity is the result of immune-stimulation. Collectively, the R8/KALA-MEND mounts a "switch-on" function that triggers signal transduction forward to the immune-stimulation analogous to an adjuvant, and consequently elicits active transcription.

Original languageEnglish
Pages (from-to)8979-8990
Number of pages12
JournalBiomaterials
Volume34
Issue number35
DOIs
Publication statusPublished - Nov 1 2013
Externally publishedYes

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Transcription
Microarray Analysis
Microarrays
Oligonucleotide Array Sequence Analysis
Nanoparticles
Dendritic Cells
DNA
Transfection
Genes
Chemical activation
Transgenes
Signal transduction
Gene encoding
Transcription factors
Antigens
Gene expression
Lipids
Peptides
Ontology
Gene Ontology

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

A DNA microarray-based analysis of immune-stimulatory and transcriptional responses of dendritic cells to KALA-modified nanoparticles. / Akita, Hidetaka; Ishii, Soichiro; Miura, Naoya; Shaheen, Sharif Mohammad; Hayashi, Yasuhiro; Nakamura, Takashi; Kaji, Noritada; Baba, Yoshinobu; Harashima, Hideyoshi.

In: Biomaterials, Vol. 34, No. 35, 01.11.2013, p. 8979-8990.

Research output: Contribution to journalArticle

Akita, Hidetaka ; Ishii, Soichiro ; Miura, Naoya ; Shaheen, Sharif Mohammad ; Hayashi, Yasuhiro ; Nakamura, Takashi ; Kaji, Noritada ; Baba, Yoshinobu ; Harashima, Hideyoshi. / A DNA microarray-based analysis of immune-stimulatory and transcriptional responses of dendritic cells to KALA-modified nanoparticles. In: Biomaterials. 2013 ; Vol. 34, No. 35. pp. 8979-8990.
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