Targeted delivery of polymer vesicles functionalized with fibronectin mimetic peptides to cancer cells

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Targeted delivery of polymer vesicles functionalized with fibronectin mimetic peptides to cancer cells

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2012-09

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Polymersomes, polymeric vesicles that self-assemble in aqueous solutions from block copolymers, have been avidly investigated in recent years as potential drug delivery agents. In this work, the feasibility of chemical conjugation of fibronectin mimetic targeting peptides (GRGDSP and PR_b) onto the surface of polymersomes is investigated, and the efficacy of these peptide functionalized polymersomes to achieve targeted delivery to cancer cells is studied. The diblock copolymer poly(ethylene oxide)-b-poly(1,2-butadiene) was synthesized and self-assembled to form polymersomes, which were subsequently functionalized with peptides using a ―click‖ conjugation reaction. Delivery efficacy of these peptide functionalized polymersomes loaded with fluorescent iii Abstract Polymersomes, polymeric vesicles that self-assemble in aqueous solutions from block copolymers, have been avidly investigated in recent years as potential drug delivery agents. In this work, the feasibility of chemical conjugation of fibronectin mimetic targeting peptides (GRGDSP and PR_b) onto the surface of polymersomes is investigated, and the efficacy of these peptide functionalized polymersomes to achieve targeted delivery to cancer cells is studied. The diblock copolymer poly(ethylene oxide)-b-poly(1,2-butadiene) was synthesized and self-assembled to form polymersomes, which were subsequently functionalized with peptides using a ―click‖ conjugation reaction. Delivery efficacy of these peptide functionalized polymersomes loaded with fluorescent markers, a chemotherapeutic (doxorubicin), or siRNA was assessed and compared. Both the efficacy and the process of delivery and internalization of peptide functionalized polymersomes were investigated for colon and breast cancer cells. PR_b functionalized polymersomes were found in all cases to significantly outperform both GRGDSP and non-functionalized polymersomes, in terms of promoting cell binding, internalization, specificity, and effective delivery. This work highlights peptide functionalized polymersomes in general, and PR_b functionalized polymersomes in specific, as a highly promising targeted delivery system.

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University of Minnesota Ph.D. dissertation. September 2012. Major: Chemical Engineering. Advisors: Efrosini Kokkoli & Frank S. Bates. 1 computer file (PDF); xv, 153 pages.

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Pangburn, Todd Owen. (2012). Targeted delivery of polymer vesicles functionalized with fibronectin mimetic peptides to cancer cells. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/143589.

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