期刊
JOURNAL OF CONTROLLED RELEASE
卷 209, 期 -, 页码 88-100出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2015.04.026
关键词
Epithelial cell adhesion molecule; Doxorubicin; Nanopolymersome; PEG-PLGA; Non-small cell lung cancer; SK-MES-1
资金
- Iran National Science Foundation [9000719]
- Mashhad University of Medical Sciences [901051]
Targeted, disease-specific delivery of therapeutic nanoparticles shows wonderful promise for transmitting highly cytotoxic anti-cancer agents. Using the reaction of non-small cell lung cancer (SK-MES-1 and A549 cell lines) as representative of other cancer types', the present study examines the effects of EpCAM-fluoropyrimidine RNA aptamer-decorated, DOX-loaded, PLGA-b-PEG nanopolymersomes that bond specifically to the extracellular domain of epithelial-cell adhesion molecules. Results demonstrate that EpCAM aptamer-conjugated DOX-NPs (Apt-DOX-NP) significantly enhance cellular nanoparticle uptake in SK-MES-1 and A549 cell lines and increase the cytotoxicity of the DOX payload as compared with non-targeted DOX-NP (P < 0.05). Additionally, Apt-DOX-NP exhibits greater tumor inhibition in nudemice bearing SK-MES-1 non-small cell lung-cancer xenografts and reduces toxicity, as determined by loss of body weight, cardiac histopathology and animal survival rate in vivo. After a single intravenous injection of Apt-DOX-NP and DOX-NPs, tumor volume decreased 60.9% and 31.4%, respectively, in SK-MES-1-xenograft nude mice compared with members of a saline-injected control group. This study proves the potential utility of Apt-DOX-NP for therapeutic application in non-small cell lung cancer. In the future, EpCAM-targeted therapies might play a key role in treating non-small cell lung cancer, the most common type of lung cancer. (C) 2015 Elsevier B.V. All rights reserved.
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