Vivek Badwaik1, Linjia Liu1, Dinara Gunasekera1, Aditya Kulkarni1, David H Thompson1. 1. 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.
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.
Targeted delivery is a key element for improving the efficiency and safety of nonviral vectors for gene therapy. We have recently developed a n>an class="Gene">CD44 receptor targeted, hyaluronic acid-adamantamethamidylbased 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: Min Sang Lee; Jung Eun Lee; Eunkyoung Byun; Nak Won Kim; Kyuri Lee; Haeshin Lee; Sang Jun Sim; Doo Sung Lee; Ji Hoon Jeong Journal: J Control Release Date: 2014-07-01 Impact factor: 9.776
Authors: Aditya Kulkarni; Ross Verheul; Kyle Defrees; Christopher J Collins; Ryan A Schuldt; Alexander Vlahu; David H Thompson Journal: Biomater Sci Date: 2013-10-01 Impact factor: 6.843