Ratiometric Singlet Oxygen Nano-optodes and Their Use for Monitoring Photodynamic Therapy Nanoplatforms

Ratiometric photonic explorers for bioanalysis with biologically localized embedding (PEBBLE) nanoprobes have been developed for singlet oxygen, using organically modified silicate (ORMOSIL) nanoparticles as the matrix. A crucial aspect of these ratiometric singlet-oxygen fluorescent probes is their minute size. The ORMOSIL nanoparticles are prepared via a sol-gel–based process and the average diameter of the resultant particles is about 160 nm. These sensors incorporate the singlet-oxygen–sensitive 9,10-dimethyl anthracene as an indicator dye and a singlet-oxygen–insensitive dye, octaethylporphine, as a reference dye for ratiometric fluorescence-based analysis. We have found experimentally that these nanoprobes have much better sensitivity than does the conventional singlet-oxygen–free dye probe, anthracene-9, 10-dipropionic acid disodium salt. The much longer lifetime of singlet oxygen in the ORMOSIL matrix, compared to aqueous solutions, in addition to the relatively high singlet oxygen solubility because of the highly permeable structure and the hydrophobic nature of the outer shell of the ORMOSIL nanoparticles, results in an excellent overall response to singlet oxygen. These nanoprobes have been used to monitor the singlet oxygen produced by “dynamic nanoplatforms” that were developed for photodynamic therapy. The singlet oxygen nanoprobes could potentially be used to quantify the singlet oxygen produced by macrophages.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75523/1/2005-05-18-RA-532.pd

Spatial analysis of malaria in Anhui province, China

<p>Abstract</p> <p>Background</p> <p>Malaria has re-emerged in Anhui Province, China, and this province was the most seriously affected by malaria during 2005–2006. It is necessary to understand the spatial distribution of malaria cases and to identify highly endemic areas for future public health planning and resource allocation in Anhui Province.</p> <p>Methods</p> <p>The annual average incidence at the county level was calculated using malaria cases reported between 2000 and 2006 in Anhui Province. GIS-based spatial analyses were conducted to detect spatial distribution and clustering of malaria incidence at the county level.</p> <p>Results</p> <p>The spatial distribution of malaria cases in Anhui Province from 2000 to 2006 was mapped at the county level to show crude incidence, excess hazard and spatial smoothed incidence. Spatial cluster analysis suggested 10 and 24 counties were at increased risk for malaria (<it>P </it>< 0.001) with the maximum spatial cluster sizes at < 50% and < 25% of the total population, respectively.</p> <p>Conclusion</p> <p>The application of GIS, together with spatial statistical techniques, provide a means to quantify explicit malaria risks and to further identify environmental factors responsible for the re-emerged malaria risks. Future public health planning and resource allocation in Anhui Province should be focused on the maximum spatial cluster region.</p

Developing optical ratiometric nanosensors/nanoprobes for biomedical applications.

This thesis presents the development of three ratiometric fluorescent PEBBLE (Photonic Explorers for Bioanalysis with Biologically Localized Embedding) nanosensors/nanoprobes: the PDMA (poly(decyl methacrylate))-based nanosensors for dissolved oxygen molecules, the ORMOSIL (organically modified silicate)-based oxygen nanosensors and the ORMOSIL-based singlet oxygen nanoprobes (the very first such ratiometric singlet oxygen nanoprobes ever developed). The PDMA oxygen nanosensors have been used for dissolved oxygen concentration measurements inside highly scattering biosamples such as human plasma. The ORMOSIL oxygen nanosensors have been successfully injected into live C6-glioma cancer cells via gene-gun delivery for real-time measurements of intracellular oxygen. Both PDMA and ORMOSIL oxygen nanosensors have demonstrated great improvements over previous oxygen PEBBLE nanosensors. The singlet oxygen nanoprobes have been utilized successfully to monitor the singlet oxygen production efficiency of dynamic nanoplatforms developed for photodynamic therapy of cancer. Furthermore, the introduction of ORMOSIL as a new PEBBLE matrix for both hydrophobic and hydrophilic dyes has significantly advanced the PEBBLE technology. This thesis also introduces a new ratiometric approach that makes the nanofabrication of PEBBLE nanosensors/nanoprobes more flexible, convenient and cheaper. The work presented indicates that these PEBBLE nanosensors/nanoprobes can be utilized in the near future for many other biomedical applications.Ph.D.Analytical chemistryApplied SciencesBiomedical engineeringPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/125282/2/3192564.pd