title: Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.
abstract: To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Dongxi
authors.initials: D
authors.lastname: Xiang
authors.affiliation: School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Shigdar
authors.affiliation: School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Wenrong
authors.initials: W
authors.lastname: Yang
authors.affiliation: School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Lin
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian, People's Republic of China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
authors.affiliation: School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D000071858:Epithelial Cell Adhesion Molecule; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D054709:Lecithins / Q000737:chemistry; D008297:Male; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D036103:Nanotechnology; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D015815:Cell Adhesion Molecules; D004337:Drug Carriers; D000071858:Epithelial Cell Adhesion Molecule; D054709:Lecithins; D058726:Nanoconjugates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D003474:Curcumin
keywords: EpCAM; PLGA-lecithin-PEG nanoparticles; aptamer; curcumin; targeted drug delivery