title: The Interactions between L-tyrosine based nanoparticles decorated with folic acid and cervical cancer cells under physiological flow.
abstract: Many anticancer drugs have been established clinically, but their efficacy can be compromised by nonspecific toxicity and an inability to reach the desired cancerous intracellular spaces. In order to address these issues, researchers have explored the use of folic acid as a targeted moiety to increase specificity of chemotherapeutic drugs. To expand upon such research, we have conjugated folic acid to functionalized poly(ethylene glycol) and subsequently decorated the surface of l-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles possess the appropriate size (100-500 nm) for internalization as shown by scanning electron microscopy and dynamic light scattering. Under simulated physiological flow, LTP nanoparticles decorated with folic acid (targeted nanoparticles) show a 10-fold greater attachment to HeLa, a cervical cancer cell line, compared to control nanoparticles and to human dermal fibroblasts. The attachment of these targeted nanoparticles progresses at a linear rate, and the strength of this nanoparticle attachment is shown to withstand shear stresses of 3.0 dyn/cm(2). These interactions of the targeted nanoparticles to HeLa are likely a result of a receptor-ligand binding, as a competition study with free folic acid inhibits the nanoparticle attachment. Finally, the targeted nanoparticles encapsulated with a silver based drug show increased efficacy in comparison to nondecorated (plain) nanoparticles and drug alone against HeLa cells. Thus, targeted nanoparticles are a promising delivery platform for developing anticancer therapies that overexpress the folate receptors (FRs).
authors.affiliation: Department of Biomedical Engineering, The University of Akron, Olson Research Center, Akron, Ohio 44325-0302, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ditto
authors.forename: Kush N
authors.initials: KN
authors.lastname: Shah
authors.forename: Nikki K
authors.initials: NK
authors.lastname: Robishaw
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Panzner
authors.forename: Wiley J
authors.initials: WJ
authors.lastname: Youngs
authors.forename: Yang H
authors.initials: YH
authors.lastname: Yun
mesh_terms: D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology / Q000378:metabolism; D004337:Drug Carriers; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D058975:Folate Receptor 1 / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D010755:Organophosphates / Q000378:metabolism*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D004337:Drug Carriers; D058975:Folate Receptor 1; D010755:Organophosphates; D011108:Polymers; C542009:tyrosine polyphosphate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D005492:Folic Acid