title: Folate Conjugated Cellulose Nanocrystals Potentiate Irreversible Electroporation-induced Cytotoxicity for the Selective Treatment of Cancer Cells.
abstract: Cellulose nanocrystals are rod-shaped, crystalline nanoparticles that have shown prom-ise in a number of industrial applications for their unique chemical and physical properties. However, investigations of their abilities in the biomedical field are limited. The goal of this study is to show the potential use of folic acid-conjugated cellulose nanocrystals in the potentiation of irreversible electroporation-induced cell death in folate receptor (FR)-positive cancers. We optimized key pulse parameters including pulse duration, intensity, and incubation time with nanoparticles prior to electroporation. FR-positive cancer cells, KB and MDA-MB-468, were preincubated with cellulose nanocrystals (CNCs) conjugated with the targeting molecule folic acid (FA), 10 and 20 min respectively, prior to application of the optimized pulse electric field (PEF), 600 and 500 V/cm respectively. We have shown cellulose nanocrystals' ability to potentiate a new technique for tumor ablation, irreversible electroporation. Pre-incubation with FA-conjugated CNCs (CNC-FA) has shown a significant increase in cytotoxicity induced by irreversible electroporation in FR-positive cancer cells, KB and MDA-MB-468. Non-targeted CNCs (CNC-COOH) did not potentiate IRE when preincubated at the same parameters as previously stated in these cell types. In addition, CNC-FA did not potentiate irreversible electroporation-induced cytotoxicity in a FR-negative cancer cell type, A549. Without changing irreversible electroporation parameters it is possible to increase the cytotoxic effect on FR-positive cancer cells by exploiting the specific binding of FA to the FR, while not causing further damage to FR-negative tissue.
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA, USA colacino@vt.edu.
authors.forename: Katelyn R
authors.initials: KR
authors.lastname: Colacino
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Arena
authors.affiliation: Macromolecules and Interfaces Institute and Department of Sustainable Biomaterials, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Shuping
authors.initials: S
authors.lastname: Dong
authors.affiliation: Macromolecules and Interfaces Institute and Department of Sustainable Biomaterials, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Maren
authors.initials: M
authors.lastname: Roman
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA, USA.
authors.forename: Rafael V
authors.initials: RV
authors.lastname: Davalos
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA, USA Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Yong W
authors.initials: YW
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D002482:Cellulose; D016503:Drug Delivery Systems / Q000379:methods*; D053672:Electrochemotherapy / Q000379:methods*; D020342:Finite Element Analysis; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D018613:Microscopy, Confocal; D053758:Nanoparticles
chemical_list: D002482:Cellulose; D005492:Folic Acid
keywords: Cancer treatment; Folate receptor; Targeted drug delivery