Publication Date

2018-03-29

Availability

Open access

Embargo Period

2018-03-29

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Chemistry (Arts and Sciences)

Date of Defense

2018-03-22

First Committee Member

Françisco M. Raymo

Second Committee Member

Roger M. Leblanc

Third Committee Member

James N. Wilson

Fourth Committee Member

James D. Baker

Abstract

Self-assembling amphiphilic macromolecular nanoparticle, with a hydrophobic inner core and hydrophilic shell, can capsulate organic dyes inside. Thus, as a result, could be a valuable delivery vehicle for biology applications. We have developed a family of polymers, as supramolecular hosts, with decyl and polyethylene glycol side chains, exhibiting different hydrophobic/hydrophilic ratio, polyethylene glycol length or molecular weight. The polymers assemble into particles in neutral buffer and capture hydrophobic BODIPY in their interior. The relationship between critical concentration, dye loading property, hydrodynamic diameter and polymer structures were investigated. These provided a guideline to design self-assembling supramolecular hosts for the encapsulation of fluorescent guests and can lead to ideal delivery vehicles for the imaging probes to target locations in biosystems. In additional, a halochromic coumarin-oxazine fluorophore was connected to the side chains of an amphiphilic polymer covalently, with folate ligands as targeting agents to MCF-7 cancer cells. The pre-fluorophores did not produce any detectable fluorescence at neutral pH, but are converted into fluorophores with red emission in acidic environment. Thus, this design offers the opportunity to highlight cancer cells selectively with high brightness and optimal contrast. We also designed a photoactivatable BODIPY with two oxazines attached. As a result, the oxazine heterocycles can be disconnected stepwise upon UV irradiation and each product exhibit different emission bands. When relative amounts of chromophores are placed in a polystyrene bead matrix, the ratio of three component can be modulated by dose of activating photons. This ratiometric strategy can be applied to write barcode inside biosystems: different regions of a same animal can be labeled with different barcodes to allow the monitoring of the spatiotemporal tracking.

Keywords

Fluorescence; Molecular Switch; Amphiphilic Polymer; Bioimaging; BODIPY; Probe

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