title: Mechanistic Insight into Receptor-Mediated Delivery of Cationic-β-Cyclodextrin:Hyaluronic Acid-Adamantamethamidyl Host:Guest pDNA Nanoparticles to CD44(+) Cells.
abstract: Targeted delivery is a key element for improving the efficiency and safety of nonviral vectors for gene therapy. We have recently developed a CD44 receptor targeted, hyaluronic acid-adamantamethamidyl based pendant polymer system (HA-Ad), capable of forming complexes with cationic β-cyclodextrins (CD-PEI(+)) and pDNA. Complexes formed using these compounds (HA-Ad:CD-PEI(+):pDNA) display high water solubility, good transfection efficiency, and low cytotoxicity. Spatial and dynamic tracking of the transfection complexes by confocal microscopy and multicolor flow cytometry techniques was used to evaluate the target specificity, subcellular localization, and endosomal escape process. Our data shows that cells expressing the CD44 receptor undergo enhanced cellular uptake and transfection efficiency with HA-Ad:CD-PEI(+):pDNA complexes. This transfection system, comprised noncovalent assembly of cyclodextrin:adamantamethamidyl-modified hyaluronic acid via host:guest interactions to condense pDNA, is a potentially useful tool for targeted delivery of nucleic acid therapeutics.
authors.affiliation: Department of Chemistry and Purdue University Center for Cancer Research, Multidisciplinary Cancer Research Facility, Bindley Bioscience Center, Purdue University , 1203 West State Street, West Lafayette, Indiana 47907, United States.
authors.forename: Vivek
authors.initials: V
authors.lastname: Badwaik
authors.affiliation: Department of Chemistry and Purdue University Center for Cancer Research, Multidisciplinary Cancer Research Facility, Bindley Bioscience Center, Purdue University , 1203 West State Street, West Lafayette, Indiana 47907, United States.
authors.forename: Linjia
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Purdue University Center for Cancer Research, Multidisciplinary Cancer Research Facility, Bindley Bioscience Center, Purdue University , 1203 West State Street, West Lafayette, Indiana 47907, United States.
authors.forename: Dinara
authors.initials: D
authors.lastname: Gunasekera
authors.affiliation: Department of Chemistry and Purdue University Center for Cancer Research, Multidisciplinary Cancer Research Facility, Bindley Bioscience Center, Purdue University , 1203 West State Street, West Lafayette, Indiana 47907, United States.
authors.forename: Aditya
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Department of Chemistry and Purdue University Center for Cancer Research, Multidisciplinary Cancer Research Facility, Bindley Bioscience Center, Purdue University , 1203 West State Street, West Lafayette, Indiana 47907, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Thompson
mesh_terms: D000218:Adamantane / Q000737:chemistry*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D011108:Polymers; D047392:beta-Cyclodextrins; D006820:Hyaluronic Acid; D004247:DNA; D000218:Adamantane
keywords: CD44 receptor; cationic β-cyclodextrin; hyaluronic acid conjugate; pDNA transfection