INVESTIGATION OF MOLECULAR FLUOROPHORE UPTAKE BY CONJUGATED POLYMER NANOPARTICLES

Aims

The aim of this work is to better understand the driving forces for molecular doping of a hydrophobic conjugated polymer. Conjugated polymer nanoparticles5 may act as models for the study of molecular transport through a medium and the eventual application of targeted drug delivery systems. Doped conjugated polymer nanoparticles may also have significant potential for sensitive fluorescence-based assays.
By varying the hydrophobicity and/or functional groups of certain laser dye molecules, we intend to study the relative amounts of fluorophore that are incorporated within polymer nanoparticles versus those molecules that merely interact with the nanoparticle surface or stay independently in solution. We intend to consider the phase-change thermodynamics of the molecules as compared to the polymers and to test whether the extent of doping of nanoparticles with small molecules can be accurately predicted.
We intend to follow the uptake of fluorophore in the following way. A given fluorophore may show spectral shifts based on dipole interactions of the excited state with its environment or due to specific fluorophore-solvent interactions . Hence the environment of a given fluorophore may be probed spectroscopically.

Background and Significance

A variety of inherited and acquired diseases may be treated through the delivery of DNA into cells under the umbrella of gene therapy. Viruses have been thought as the carrier of choice because of their ability to enter the cell. However, as a result of long-term safety, inert polymer materials are being considered the future gene carriers of choice. Drug release by polymers may not be restricted to gene therapy but in general the release of a drug from an inert polymer medium will be a critical factor for the effectiveness of the treatment.

Conjugated polymers have been shown to demonstrate optical absorption and fluorescence characteristics that vary greatly depending on the conformation of the polymer . It has also been shown that, through clever variation of solvent quality, an aqueous dispersion of nanoparticles of such polymers can be formed . These nanoparticles can be formed with a range of diameters (10-30nm). We believe that the polymer may act as an important model system for drug delivery vehicles. We believe that the unique properties of this polymer provide an excellent analog for studying the diffusion of molecules into and out of an inert drug delivery system, as a function of the hydrophobicity of a surrounding membrane, protein or solvent.

We propose a study of the incorporation of a broad range of molecular fluorophores into these polymer nanoparticles. My goal is to understand the driving forces for molecular incorporation by varying the hydrophobicity of the molecules and/or functional groups belonging to these fluorophores. We intend to study the relative amounts of fluorophore that are incorporated within the polymer nanoparticle versus those molecules that merely interact with the nanoparticle surface. We intend to consider the phase-change thermodynamics of the molecules as compared to the polymers and to test whether the extent of doping of nanoparticles with small molecules can be accurately predicted.

As precedent, Wu et al5 have shown nanoparticles made of different conjugated polymers where energy transfer from a blue-emitting polymer host to a red-emitting polymer dopant is highly efficient and quantitatively described. We propose that similar energy transfer will occur from polymer hosts to molecular dopants and so uptake of molecular fluorophores will be independently measurable by studying fluorescence intensity changes of the dopant molecule.

We intend to follow the uptake of fluorophore in the following way. A given fluorophore may show spectral shifts based on dipole interactions of the excited state with its environment or due to specific fluorophore-solvent interactions . Hence the environment of a given fluorophore may be probed spectroscopically. The uptake of a molecule by the polymer will provide a drastically different environment as compared to the environment seen at the surface of the polymer or to the environment seen when that fluorophore is freely solvated independently in the solvent itself.

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Lakowicz, J.; "Principles of Fluorescence Spectroscopy", 2004, 185-210, Springer Science+Business Media, Inc., New York.

Leong, K. W.; "Polymeric controlled nucleic acid delivery", MRS Bulletin Proceedings, September 2005.

Michaels, A. S.; "Applications of the theory of molecular transport in polymers to the design of controlled drug delivery systems." Polymer Preprints (American Chemical Society, Division of Polymer Chemistry) 1979, 20, 332-5.

Collison, C.J.; Rothberg, L.J.; Treemaneekarn, V.; Li, Y.; "Conformational Effects on the photophysics of conjugated polymers: A two species model for MEH-PPV spectroscopy and dynamics", Macromolecules 2001, 34, 2346-2352.

Wu, C.; Peng, H.; Jiang, Y.; McNeill, J.; "E nergy transfer mediated fluorescence from blended conjugated polymer nanoparticles", 14154.

Lakowicz, J.; "Principles of Fluorescence Spectroscopy", 2004, 185-210, Springer Science+Business Media, Inc., New York.