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Polymer vesicle based cell mimetics for use in immune therapy.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Robbins, Gregory Patrick.
- Language:
- English
- Subjects (All):
- Chemical engineering.
- Biomedical engineering.
- 0541.
- 0542.
- Penn dissertations--Chemical and biomolecular engineering.
- Chemical and biomolecular engineering--Penn dissertations.
- Local Subjects:
- Penn dissertations--Chemical and biomolecular engineering.
- Chemical and biomolecular engineering--Penn dissertations.
- 0541.
- 0542.
- Physical Description:
- 279 pages
- Contained In:
- Dissertation Abstracts International 71-01B.
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- Polymersomes are fully synthetic lamellar structures that mimic the cell membrane. These biocompatible vesicles are mechanically strong and have tunable properties such as elastic modulus and membrane thickness, making them ideal platforms on which to build drug and imaging contrast agent delivery systems. In this work, we mimic several aspects of immune cells, the ability to bind selectively and avidly to specific substrates and the ability to encapsulate proteins and release encapsulates in response to external cues. These properties can be built into the polymersome to create system that can be used in vivo to interact specifically with immune cells. Parallel plate flow chamber experiments are used to show that two-ligands can be attached to vesicle surfaces to tune the adhesivity under flow. These ligands can be attached to vesicle surfaces at high site densities, and the ratio of ligands on the vesicle surfaces can be tuned by adjusting the ratio of ligands present during association with vesicles. Flow experiments over monolayers of inflamed and quiescent HUVEC cells show that these two-ligand vesicles adhere to inflamed cells compared to quiescent cells with greater selectivity and avidity than to single-ligand coated vesicles. Reflective interference contrast microscopy and flow chamber experiments are then used to examine the influence of membrane deformability on vesicle adhesion. This work shows that membrane deformability affects vesicle recruitment to substrates, but this change does not affect the rolling velocities of adhesive vesicles. Next, we use confocal microscopy and flow cytometry to show that ferritin protein can be encapsulated in vesicles, and the affect of ferritin encapsulation on membrane rheology is determined using micropipette aspiration. Finally, confocal microscopy and fluorescent illumination is used to show that co-encapsulation of a protein and a porphyrin fluorophore imparts vesicles with a photo-labile property that can be used to facilitate release of encapsulated cargo in response to external cues. This photo-responsive property is thought to arise from differential thermal expansivities of the individual membrane leaflets.
- Notes:
- Thesis (Ph.D. in Chemical and Biomolecular Engineering) -- University of Pennsylvania, 2009.
- Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0493.
- Adviser: Daniel A. Hammer.
- Local Notes:
- School code: 0175.
- ISBN:
- 9781109585308
- Access Restriction:
- Restricted for use by site license.
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