Document Detail


Ionically crosslinked Ad/chitosan nanocomplexes processed by electrospinning for targeted cancer gene therapy.
MedLine Citation:
PMID:  20637814     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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 140nm, and the surface charge was 2.1mV compared to -4.9mV 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.
Authors:
Yeonah Park; Eunah Kang; Oh-Joon Kwon; Taewon Hwang; Hongkwan Park; Jung Min Lee; Jung Hyun Kim; Chae-Ok Yun
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Publication Detail:
Type:  Journal Article     Date:  2010-07-15
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  148     ISSN:  1873-4995     ISO Abbreviation:  J Control Release     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2011-05-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  75-82     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Graduate Program for Nanomedical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Project for Medical Sciences and Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
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