title: Epithelial cell adhesion molecule aptamer conjugated PEG-PLGA nanopolymersomes for targeted delivery of doxorubicin to human breast adenocarcinoma cell line in vitro.
abstract: Targeted delivery of anti-cancer agents exclusively to tumor cells introduces an attractive strategy because it increases the therapeutic index compared with untargeted drugs. Aptamer conjugated nanoparticles that can specifically bind to the proteins on a tumor cell surface are capable nanoscale delivery systems for enhancing cellular uptake of chemotherapeutic agents. The epithelial cell adhesion molecule (EpCAM) as a cancer stem cell marker emerges as a versatile target for aptamer-based cancer therapy due to its high expression level in various adenocarcinoma cell lines and its very low expression level in normal cells. We developed EpCAM-targeted PEG-PLGA nanopolymersomes by covalently coupling the EpCAM aptamer to the surface of nanopolymersomes loaded with the anticancer agent doxorubicin via pH gradient method. The results indicated that doxorubicin was entrapped in PEG-PLGA nanopolymersomes with encapsulation efficiency and loading content of 91.25±4.27% and 7.3±0.34%, respectively. Over a period of 5 days, up to 8% of the DOX was released through this system. The doxorubicin-loaded aptamer conjugated nanopolymersomes exhibited efficient cell uptake and internalization, and were significantly more cytotoxic (P<0.01) toward EpCAM-positive tumor cells (MCF-7) than non-targeted nanopolymersomes. Our data suggest that EpCAM-targeted nanopolymersomes will lead to an improved therapeutic index of doxorubicin to EpCAM positive cancer cells.
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mona
authors.initials: M
authors.lastname: Alibolandi
authors.affiliation: 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.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
authors.affiliation: 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.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sadeghi
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: abnouskh@mums.ac.ir.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: hadizadehf@mums.ac.ir.
authors.forename: Farzin
authors.initials: F
authors.lastname: Hadizadeh
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001692:Biological Transport; D001943:Breast Neoplasms / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Aptamer; EpCAM; Nanopolymersomes; PEG–PLGA; Targeted drug delivery