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In Vitro and in Vivo Evaluation of Therapy Targeting Epithelial-Cell Adhesion-Molecule Aptamers for Non-Small Cell Lung Cancer Publisher Pubmed



Alibolandi M1 ; Ramezani M2, 3 ; Abnous K2 ; Sadeghi F4, 5 ; Atyabi F6 ; Asouri M7 ; Ahmadi AA7 ; Hadizadeh F1
Authors
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Authors Affiliations
  1. 1. Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 9196773117, Mashhad, Iran
  2. 2. Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  3. 3. Nanothechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  4. 4. Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  5. 5. Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  6. 6. Nanothechnology Research Center, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. North Research Center, Pasteur Institute of Iran, Amol, Iran

Source: Journal of Controlled Release Published:2015


Abstract

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 nude mice 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. © 2015 Elsevier B.V.