Ionically crosslinked Ad/chitosan nanocomplexes processed by electrospinning for targeted cancer gene therapy

Yeonah Park, Eunah Kang, Oh Joon Kwon, Taewon Hwang, Hongkwan Park, Jung Min Lee, Jung-Hyun Kim, Chae Ok Yun

Research output: Contribution to journalArticle

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Abstract

For effective cancer gene therapy, systemic administration of tumor-targeting adenoviral (Ad) complexes is critical for delivery to both primary and metastatic lesions. Electrospinning was used to generate nanocomplexes of Ad, chitosan, poly(ethylene glycol) (PEG), and folic acid (FA) for effective FA receptor-expressing tumor-specific transduction. The chemical structure of the Ad/chitosan-PEG-FA nanocomplexes was characterized by NMR and FT-IR, and the diameter and surface charge were analyzed by dynamic light scattering and zeta potentiometry, respectively. The average size of Ad/chitosan-PEG-FA nanocomplexes was approximately 140. nm, and the surface charge was 2.1. mV compared to - 4.9 mV for naked Ad. Electron microscopy showed well-dispersed, individual Ad nanocomplexes without aggregation or degradation. Ad/chitosan nanocomplexes retained biological activity without impairment of the transduction efficiency of naked Ad. The transduction efficiency of Ad/chitosan-PEG-FA was increased as a function of FA ratio in FA receptor-expressing KB cells, but not in FA receptor-negative U343 cells, demonstrating FA receptor-targeted viral transduction. In addition, the transduction efficiency of Ad/chitosan-PEG-FA was 57.2% higher than chitosan-encapsulated Ad (Ad/chitosan), showing the superiority of FA receptor-mediated endocytosis for viral transduction. The production of inflammatory cytokine, IL-6 from macrophages was significantly reduced by Ad/chitosan-PEG-FA nanocomplexes, implying the potential for use in systemic administration. These results clearly demonstrate that cancer cell-targeted viral transduction by Ad/chitosan-PEG-FA nanocomplexes can be used effectively for metastatic tumor treatment with reduced immune reaction against Ad.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalJournal of Controlled Release
Volume148
Issue number1
DOIs
Publication statusPublished - 2010 Nov 20

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Neoplasm Genes
Chitosan
Folic Acid
Genetic Therapy
Neoplasms
Potentiometry
KB Cells
Ethylene Glycol
Endocytosis
Interleukin-6
Electron Microscopy
Macrophages

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Park, Yeonah ; Kang, Eunah ; Kwon, Oh Joon ; Hwang, Taewon ; Park, Hongkwan ; Lee, Jung Min ; Kim, Jung-Hyun ; Yun, Chae Ok. / Ionically crosslinked Ad/chitosan nanocomplexes processed by electrospinning for targeted cancer gene therapy. In: Journal of Controlled Release. 2010 ; Vol. 148, No. 1. pp. 75-82.
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abstract = "For effective cancer gene therapy, systemic administration of tumor-targeting adenoviral (Ad) complexes is critical for delivery to both primary and metastatic lesions. Electrospinning was used to generate nanocomplexes of Ad, chitosan, poly(ethylene glycol) (PEG), and folic acid (FA) for effective FA receptor-expressing tumor-specific transduction. The chemical structure of the Ad/chitosan-PEG-FA nanocomplexes was characterized by NMR and FT-IR, and the diameter and surface charge were analyzed by dynamic light scattering and zeta potentiometry, respectively. The average size of Ad/chitosan-PEG-FA nanocomplexes was approximately 140. nm, and the surface charge was 2.1. mV compared to - 4.9 mV for naked Ad. Electron microscopy showed well-dispersed, individual Ad nanocomplexes without aggregation or degradation. Ad/chitosan nanocomplexes retained biological activity without impairment of the transduction efficiency of naked Ad. The transduction efficiency of Ad/chitosan-PEG-FA was increased as a function of FA ratio in FA receptor-expressing KB cells, but not in FA receptor-negative U343 cells, demonstrating FA receptor-targeted viral transduction. In addition, the transduction efficiency of Ad/chitosan-PEG-FA was 57.2{\%} higher than chitosan-encapsulated Ad (Ad/chitosan), showing the superiority of FA receptor-mediated endocytosis for viral transduction. The production of inflammatory cytokine, IL-6 from macrophages was significantly reduced by Ad/chitosan-PEG-FA nanocomplexes, implying the potential for use in systemic administration. These results clearly demonstrate that cancer cell-targeted viral transduction by Ad/chitosan-PEG-FA nanocomplexes can be used effectively for metastatic tumor treatment with reduced immune reaction against Ad.",
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Ionically crosslinked Ad/chitosan nanocomplexes processed by electrospinning for targeted cancer gene therapy. / Park, Yeonah; Kang, Eunah; Kwon, Oh Joon; Hwang, Taewon; Park, Hongkwan; Lee, Jung Min; Kim, Jung-Hyun; Yun, Chae Ok.

In: Journal of Controlled Release, Vol. 148, No. 1, 20.11.2010, p. 75-82.

Research output: Contribution to journalArticle

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AU - Kang, Eunah

AU - Kwon, Oh Joon

AU - Hwang, Taewon

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AU - Lee, Jung Min

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AU - Yun, Chae Ok

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