Chemistry Reference
In-Depth Information
Two unique features of dendritic architecture are especially appealing for design of
imaging tracers: the ability to encapsulate and “protect” the central coremotif, and the
ability to enhance a selectedmolecular property throughmultiplying functionalities at
the dendrimer periphery (or in the interior). Over the years, dendritic encapsulation
has received tremendous attention in different areas of chemistry [3,4]. For design of
imaging agents it offers a convenient way to isolate the sensor moiety from
components of biological systems, improve its solubility and minimize potential
toxicity. On the other hand, the ability to place multiple functional units at the
periphery of a dendrimer makes it possible to modulate the core nanoenvironment,
and by doing so fine-tune the core properties to meet the requirements of the imaging
application. In addition, peripheral modification with groups of different charge and
hydrophobicity provides a method for controlling solubility, in vivo distribution and
excretability of imaging agents.
In this chapter we focus on the construction of molecular probes for imaging
oxygen in biological systems, which has been the central topic of our research in the
past several years. Phosphorescent imaging probes are based on porphyrin dendri-
mers—a class of functional macromolecules reminiscent of heme-containing pro-
teins, in which hemes are buried deep inside polypeptide macrostructures and
protected from direct interactions with solvent and solutes. Mimicking the protein
matrix, hydrophobic dendritic wedges in porphyrin dendrimers modulate properties
of the encapsulated cores and control the accessibility of the cores to small molecules.
Not surprisingly, porphyrin dendrimers have continuously attracted attention in light
harvesting, electron transfer (ET), host-guest chemistry, photodynamic therapy and
many other areas of research. Their synthesis and use in these applications have been
recently covered in excellent comprehensive reviews [5,6].
In porphyrin-based oxygen probes, dendrimers serve to provide well-defined
nanoenvironments for optically active cores, that is, Pt or Pd porphyrins, and to create
an interface between phosphorescent cores of the probes and biological systems. Most
importantly, folded dendritic matrix enables control over the kinetic accessibility of
metalloporphyrins for small quencher molecules (oxygen)—a property much needed
for tuning the sensitivity and the dynamic range of the oxygen measurement method.
Below, after a brief description of the principles of the oxygen imaging method
based on quenching of phosphorescence, we formulate the requirements for in vivo
oxygen probes and describe molecular oxygen sensors-based Pd and Pt porphyrin
(PtP) dendrimers. We then address probes designed specifically for two-photon (2P)
oxygenmicroscopy—amode of oxygen imaging in vivo in three dimensions with near
diffraction-limited resolution. Examples of applications of porphyrin dendrimers in
oxygen sensing and imaging are featured in the end of the chapter.
14.2 PRINCIPLES OF THE PHOSPHORESCENCE QUENCHING
METHOD AND REQUIREMENTS TO IN VIVO OXYGEN PROBES
Methods for measurement and imaging of oxygen play a central role in quantification of
cellular metabolism and understanding tissue physiology [7,8]. A number of approaches
