Dendritic Phosphorescent Probes for Oxygen Imaging in Biological Systems

Abstract

Oxygen levels in biological systems can be measured by the phosphorescence quenching method using probes with controllable quenching parameters and defined biodistributions. We describe a general approach to the construction of phosphorescent nanosensors with tunable spectral characteristics, variable degrees of quenching, and a high selectivity for oxygen. The probes are based on bright phosphorescent Pt and Pd complexes of porphyrins and symmetrically π-extended porphyrins (tetrabenzoporphyrins and tetranaphthoporphyrins). π-Extension of the core macrocycle allows tuning of the spectral parameters of the probes in order to meet the requirements of a particular imaging application (e.g., oxygen tomography versus planar microscopic imaging). Metalloporphyrins are encapsulated into poly(arylglycine) dendrimers, which fold in aqueous environments and create diffusion barriers for oxygen, making it possible to regulate the sensitivity and the dynamic range of the method. The periphery of the dendrimers is modified with poly(ethylene glycol) residues, which enhance the probe's solubility, diminish toxicity, and help prevent interactions of the probes with the biological environment. The probe's parameters were measured under physiological conditions and shown to be unaffected by the presence of biomacromolecules. The performance of the probes was demonstrated in applications, including in vivo microscopy of vascular pO 2 in the rat brain.

Indicators for optical oxygen sensors

“…Imaging of oxygen distribution has become a popular technique in different fields of application such as biomedicine [158,257], marine microbiology [75,86], and biological systems (intra-and extracellular oxygen distribution) [57,130].…”

Non-invasive monitoring of skin inflammation using an oxygen-sensing paint-on bandage

“…The relationship between emission intensity and oxygen concentration (pO 2 ) is described by the Stern-Volmer equation, shown below [11]. This phenomenon of oxygen-dependent quenching of phosphorescence has been exploited frequently for various biomedical applications [12][13][14][15][16][17][18][19]. As has been described by Wilson and Vinogradov, this process is highly efficient and responds instantaneously to fluctuations or perturbations in oxygen concentration.…”

Nanoparticles for Brain-Specific Drug and Genetic Material delivery, Imaging and Diagnosis

“…PAMAM dendrimer generations 1-8 have been functionalized with gadolinium and rhodamine B for both magnetic resonance and fluorescence imaging of malignant gliomas. Several more attempts have been made to generate dendrimer-based imaging nanoprobes, including a dendrimer-PEG copolymer-based architecture for fluorescence sensing, imaging for the first time extracellular pH in the brain in a mouse epilepsy model [68]; a dendrimer-based optical/paramagnetic nanoprobe, which showed a capability to circumvent the BBB and yielded high sensitivity images of brain tumors in vivo [69] and the use of dendritic phosphorescent probes for oxygen imaging in rat brains [70].…”