Fluorescent dyes and nanoparticles are widely used in chemistry, biology, and medicine but suffer from poor photostability or toxicity (nanoparticles). The goal of this proposal is to create ultra-stable, monovalent, organic nanoparticles or organic coated metallic/silicon nanoparticles (<6 nm size) using recently discovered chemistry that allows polyglycerol dendrimers and hyperbranched polymers to be tightly cross-linked around a core structure. The polyglycerol surfaces will be allylated and cross-linked using the ring-closing metathesis (RCM) reaction, followed by surface dihydroxylation to create a water-soluble particle. This chemistry is colloquially referred to as "multi-layer shrink-wrapping." The goal of the shrink-wrapping is to chemically isolate the fluorophore or preexisting nanoparticle and thus: (1) prevent dye aggregation, which often diminishes its performance, (2) prevent its undesired association with membranes and other biomolecules, and, most importantly, (3) reduce or eliminate photobleaching, and (4) stabilize existing nanoparticles with a dense, biocompatible sheath. We propose that through extreme isolation of the fluorophore or nanoparticle it may function indefinitely, thereby enabling a range of applications not previously possible. The fluorescent nanoparticles, which are designed to be fully biocompatible, can exhibit a range of excitation and emission wavelengths.

Public Health Relevance

Fluorescent dyes and nanoparticles are widely used in medical diagnostics and for understanding chemical and biological processes at the molecular and cellular level. However, the dyes degrade rapidly upon irradiation and many nanoparticles contain toxic metals or are inherently toxic because of their surface coating. We propose a new strategy for preparing organic-based, ultra-stable and biocompatible fluorescent nanoparticles.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM087448-04
Application #
8412779
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lewis, Catherine D
Project Start
2010-01-01
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2014-12-31
Support Year
4
Fiscal Year
2013
Total Cost
$261,133
Indirect Cost
$89,170
Name
University of Illinois Urbana-Champaign
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Yang, Si Kyung; Shi, Xinghua; Park, Seongjin et al. (2013) A dendritic single-molecule fluorescent probe that is monovalent, photostable and minimally blinking. Nat Chem 5:692-7
Zill, Andrew; Rutz, Alexandra L; Kohman, Richie E et al. (2011) Clickable polyglycerol hyperbranched polymers and their application to gold nanoparticles and acid-labile nanocarriers. Chem Commun (Camb) 47:1279-81