title: Bimodal Targeting Using Sulfonated, Mannosylated PEI for Combined Gene Delivery and Photodynamic Therapy.
abstract: Photodynamic therapy (PDT) and gene delivery have both been used to target both cancer cells and tumor-associated macrophages (TAMs). Given the complex nature of tumor tissue, there could be merit in combining these strategies simultaneously. In this study, we developed a bimodal targeting approach to both cancer cells and macrophages, employing materials conducive to both gene delivery and PDT. Polymers libraries were created that consisted of cationic polyethyleneimine (PEI) conjugated to the photosensitizer pyropheophorbide-a, with sulfonation (to target selectin-expressing cells) and mannosylation (to target TAMs). Polyplexes, consisting of these polymers electrostatically bound to DNA, were analyzed for transfection efficacy and cytotoxicity toward epithelial cells and macrophages to assess dual-targeting. This study provides preliminary proof of principle for using modified PEI for targeted gene delivery and PDT.
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Upendra
authors.initials: U
authors.lastname: Chitgupi
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Mingfu
authors.identifier: 0000-0002-0169-613X
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY.|Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shao
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Marie
authors.initials: M
authors.lastname: Beitelshees
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Myles Joshua
authors.initials: MJ
authors.lastname: Tan
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Sriram
authors.initials: S
authors.lastname: Neelamegham
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Pfeifer
authors.affiliation: Abcombi Biosciences Inc., Buffalo, NY.
authors.forename: Charles
authors.initials: C
authors.lastname: Jones
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY.|Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Lovell
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D004247:DNA / Q000737:chemistry; D004847:Epithelial Cells / Q000187:drug effects; D049449:Luminescence; D008264:Macrophages / Q000187:drug effects; D008358:Mannose / Q000737:chemistry*; D009029:Mosaic Viruses / Q000235:genetics; D010778:Photochemotherapy; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055672:Static Electricity; D013450:Sulfones / Q000737:chemistry*; D014162:Transfection
chemical_list: D013450:Sulfones; D011094:Polyethyleneimine; D004247:DNA; D008358:Mannose