Tumor-targeting transferrin nanoparticles for systemic polymerized siRNA delivery in tumor-bearing mice

Ji Young Yhee, So Jin Lee, Sangmin Lee, Seungyong Song, Hyun Su Min, Sun Woong Kang, Sejin Son, Seo Young Jeong, Ick Chan Kwon, Sun Hwa Kim, Kwang Meyung Kim

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Transferrin (TF) is widely used as a tumor-targeting ligand for the delivery of anticancer drugs because the TF receptor is overexpressed on the surface of various fast-growing cancer cells. In this article, we report on TF nanoparticles as an siRNA delivery carrier for in vivo tumor-specific gene silencing. To produce siRNA carrying TF nanoparticles (NPs), both TF and siRNA were chemically modified with sulfhydryl groups that can build up self-cross-linked siRNA-TF NPs. Self-polymerized 5′-end thiol-modified siRNA (poly siRNA, psi) and thiolated transferrin (tTF) were spontaneously cross-linked to form stable NPs (psi-tTF NPs) under optimized conditions, and they could be reversibly degraded to release functional monomeric siRNA molecules under reductive conditions. Receptor-mediated endocytosis of TF induced rapid tumor-cell-specific uptake of the psi-tTF NPs, and the internalized NPs resulted in a downregulation of the target protein in red-fluorescent-protein-expressing melanoma cancer cells (RFP/B16F10) with negligible cytotoxicity. After systemic administration, the psi-tTF NPs showed marked accumulation at the tumor, leading to successful target-gene silencing in vivo. This psi-tTF NP system provided a safe and effective strategy for in vivo systemic siRNA delivery for cancer therapy.

Original languageEnglish
Pages (from-to)1850-1860
Number of pages11
JournalBioconjugate Chemistry
Volume24
Issue number11
DOIs
Publication statusPublished - 2013 Nov 20

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Bearings (structural)
Transferrin
Nanoparticles
Small Interfering RNA
Tumors
Neoplasms
Gene Silencing
Genes
Cells
Proteins
Cytotoxicity
Transferrin Receptors
Endocytosis
Ligands
Sulfhydryl Compounds

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

Tumor-targeting transferrin nanoparticles for systemic polymerized siRNA delivery in tumor-bearing mice. / Yhee, Ji Young; Lee, So Jin; Lee, Sangmin; Song, Seungyong; Min, Hyun Su; Kang, Sun Woong; Son, Sejin; Jeong, Seo Young; Kwon, Ick Chan; Kim, Sun Hwa; Kim, Kwang Meyung.

In: Bioconjugate Chemistry, Vol. 24, No. 11, 20.11.2013, p. 1850-1860.

Research output: Contribution to journalArticle

Yhee, JY, Lee, SJ, Lee, S, Song, S, Min, HS, Kang, SW, Son, S, Jeong, SY, Kwon, IC, Kim, SH & Kim, KM 2013, 'Tumor-targeting transferrin nanoparticles for systemic polymerized siRNA delivery in tumor-bearing mice', Bioconjugate Chemistry, vol. 24, no. 11, pp. 1850-1860. https://doi.org/10.1021/bc400226b
Yhee, Ji Young ; Lee, So Jin ; Lee, Sangmin ; Song, Seungyong ; Min, Hyun Su ; Kang, Sun Woong ; Son, Sejin ; Jeong, Seo Young ; Kwon, Ick Chan ; Kim, Sun Hwa ; Kim, Kwang Meyung. / Tumor-targeting transferrin nanoparticles for systemic polymerized siRNA delivery in tumor-bearing mice. In: Bioconjugate Chemistry. 2013 ; Vol. 24, No. 11. pp. 1850-1860.
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