? The development of artificial cells that have the adhesive properties of leukocytes and can carry optical imaging agents that can peer deep within tissues would be enormously useful for the non-invasive monitoring and treatment of disease, such as inflammation. Here, we propose to construct a novel artificial cell using polymer vesicles (polymersomes) as the underlying structural element. Polymersomes are vesicles in which self-assemblying block copolymers form the membrane; since the polymers can be designed synthetically to have different molecular weights and architectures, the material properties of the artificial cell can be tuned. The membrane thickness of the polymer vesicles is much larger than that of phospholipid vesicles, owing to the size of the polymers that compose the membrane, which allows space for the storage of large, hydrophobic molecules, such as imaging agents. We endeavor to use polymersomes to make an artificial leukocyte, by functionalizing the surface groups of the polymer membrane with leukocyte-like adhesive ligands, and measuring the performance of these cells in flow chambers to mimic the dynamic environment of the microvascularture. We will tune the material properties of the membrane to make the polymersomes tougher by using large molecular polymers or by crosslinking the polymers, with the goal to match the adhesive properties of leukocytes. In addition, we will employ the synthetic expertise of the Bates laboratory to synthesize a wide range of block copolymers to engineer the biodegradability, material strength and chemical reactivity of the polymersome membrane. Further, we will incorporate novel near-infrared superfluor poly-porphyrin dyes (NIRFs) synthesized in the Therien laboratory, which, depending on their size and chemical functionality, can be excited and emit in the near-infrared. Ultimately, the optical properties of these dyes will allow for deep tissue penetration of optical signals.
The aims of this proposal are: 1) to make leuko-polymersomes, by functionalizing polymersomes with the two key adhesion molecules found on leukocytes, and measure the dynamics of polymersome adhesion under flow; 2) to engineer the material properties of the membrane, through polymer synthesis, to modulate the adhesiveness of the polymersomes; and 3) to incorporate a spectrum of large, hydrophobic near-IR dyes within the membrane of functionalized polymer vesicles, and verify their incorporation does not interfere with the adhesion dynamics of the polymer vesicles in a flow chamber. ? ?

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Diagnostic Imaging Study Section (DMG)
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Moy, Peter
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University of Pennsylvania
Engineering (All Types)
Schools of Engineering
United States
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Qi, Wei; Ghoroghchian, P Peter; Li, Guizhi et al. (2013) Aqueous self-assembly of poly(ethylene oxide)-block-poly(?-caprolactone) (PEO-b-PCL) copolymers: disparate diblock copolymer compositions give rise to nano- and meso-scale bilayered vesicles. Nanoscale 5:10908-15
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