Bimodal Targeting Using Sulfonated,Mannosylated PEI for Combined Gene Delivery and Photodynamic Therapy |
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| Authors: | Upendra Chitgupi Yi Li Mingfu Chen Shuai Shao Marie Beitelshees Myles Joshua Tan Sriram Neelamegham Blaine A. Pfeifer Charles Jones Jonathan F. Lovell |
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| Affiliation: | 1. Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY;2. Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY;3. Abcombi Biosciences Inc., Buffalo, NY |
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| 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. |
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