In vitro and in vivo evaluation of therapy targeting epithelial-cell adhesion-molecule aptamers for non-small cell lung cancer.
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.
Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Mona
M
Alibolandi
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanothechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Mohammad
M
Ramezani
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Khalil
K
Abnous
Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Fatemeh
F
Sadeghi
Nanothechnology Research Center, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Fatemeh
F
Atyabi
North Research Center, Pasteur Institute of Iran, Amol, Iran.
Mohsen
M
Asouri
North Research Center, Pasteur Institute of Iran, Amol, Iran.
Ali Asghar
AA
Ahmadi
Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: hadizadehf@mums.ac.ir.
Farzin
F
Hadizadeh
D000951:Antigens, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D000071858:Epithelial Cell Adhesion Molecule; D004912:Erythrocytes / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D011743:Pyrimidines; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D004317:Doxorubicin
Doxorubicin; Epithelial cell adhesion molecule; Nanopolymersome; Non-small cell lung cancer; PEG–PLGA; SK-MES-1