Synchrotron radiation based Fourier transform IR (SR‐FTIR) spectromicroscopy allows the study of individual living cells with a high signal to noise ratio. Here we report the use of the SR‐FTIR technique to investigate changes in IR spectral features from individual human lung fibroblast (IMR‐90) cells in vitro at different points in their cell cycle. Clear changes are observed in the spectral regions corresponding to proteins, DNA, and RNA as a cell changes from the G1‐phase to the S‐phase and finally into mitosis. These spectral changes include markers for the changing secondary structure of proteins in the cell, as well as variations in DNA/RNA content and packing as the cell cycle progresses. We also observe spectral features that indicate that occasional cells are undergoing various steps in the process of cell death. The dying or dead cell has a shift in the protein amide I and II bands corresponding to changing protein morphologies, and a significant increase in the intensity of an ester carbonyl CO peak at 1743 cm−1 is observed. © John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 57: 329‐335, 2000

The threat of a dirty bomb or other major radiological contamination presents a danger of largescale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use. Using a biomimetic approach based on the similar biochemical properties of plutonium(IV) and iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been designed and are unrivaled in terms of actinide-affinity, selectivity and efficiency. A perspective on the preclinical development of two hydroxypyridonate actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is presented. The chemical syntheses of both candidate compounds have been optimized for scale-up. Baseline preparation and analytical methods suitable for manufacturing large amounts have been established. Both ligands show much higher actinide-removal efficacy than the currently approved agent, diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is observed in cells derived from three different human tissue sources treated in vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated in rats when orally administered daily at high doses (> 100 μmol kg −1 day −1 ) over 28 days under good laboratory practice (GLP) guidelines. Both compounds are on an accelerated development pathway towards clinical use.

The low density lipoprotein (LDL) receptor has been shown to be upregulated in GBM tumor cells and is therefore a potential molecular target for the delivery of therapeutic agents. A synthetic nano-LDL (nLDL) particle was developed and tested to determine its utility as a drug Collectively these data strongly suggest that the synthetic nano-LDLs described here are taken up by LDLR and can serve as a drug delivery vehicle for targeting GBM tumors via the LDLR.3

Synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectromicroscopy is a newly emerging analytical tool capable of monitoring the biochemistry within an individual living mammalian cell in real time. This unique technique provides infrared (IR) spectra, hence chemical information, with high signal-to-noise at spatial resolutions as fine as 3 to 10 microns. Mid-IR photons are too low in energy (0.05 -0.5 eV) to either break bonds or to cause ionization, and the synchrotron IR beam has been shown to produce minimal sample heating. However, an important question remains, "Does the intense synchrotron beam induce any cytotoxic effects in living cells?" In this work, we present the results from a series of standard biological assays to evaluate any shortand/or long-term effects on cells exposed to the synchrotron radiation-based infrared (SR-IR) beam. Cell viability was tested using alcian blue dye-exclusion and colony formation assays. Cell-cycle progression was tested with bromodeoxyuridine (BrdU) uptake during DNA synthesis. Cell metabolism was tested using an MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. All control, 5-, 10-, and 20-minute SR-IR exposure tests (267 total and over 1000 controls) show no evidence of cytotoxic effects. Concurrent infrared spectra obtained with each experiment confirm no detectable chemistry changes between control and exposed cells.

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