Most bionanotechnology-based agents require careful control of surface properties to improve vascular circulation time, control delivery characteristics and provide biocompatibility, especially when used for diagnostics or therapy. The number and type of protective and targeting ligands modulate the interactions of such bionanoparticles with living systems. A method for quantifying the number of ligands associated with the surface of a bionanoparticle would be a useful tool. Here, label-free methods of conjugate quantification are described. These approaches circumvent the potentially disadvantageous surface packing defects introduced by labels used in previous methods. Conjugated PEG-S ligands were quantified using 1H nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma mass spectroscopy (ICP-AES). Normalized NMR and ICP-AES enumeration of conjugated ligands aligned with predictions based on a previously determined molecular footprint. The ligand packing density significantly decreases as available particulate surface area decreases for particle sizes from 100 nm to 5 nm. Steric hindrance and packing inefficiencies are presumed to decrease ligand binding per unit surface area for small particle diameters relative to larger particles. In addition, the packing density begins to become more constant for sizes ranging from 100 nm to 250 nm. PEG packing in this system is most efficient on particle diameters of approximately the erected length of the conjugated polymer. These results imply that the potential for maximizing bionanoparticulate effectiveness lies in the careful design and knowledge of the loading and packing profile of the protecting or targeting ligands that will be loaded on the desired particulate platform.
Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12112009-181052 |
Date | 15 December 2009 |
Creators | Bell, Charleson Sherard |
Contributors | Dr. Hak-Joon Sung, PhD, Dr. Todd D. Giorgio, PhD |
Publisher | VANDERBILT |
Source Sets | Vanderbilt University Theses |
Language | English |
Detected Language | English |
Type | text |
Format | application/pdf |
Source | http://etd.library.vanderbilt.edu//available/etd-12112009-181052/ |
Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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