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      Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance.

      Proceedings of the National Academy of Sciences of the United States of America
      Animals, Cell Line, Tumor, Female, Gold, chemistry, Humans, Hyperthermia, Induced, Infrared Rays, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, methods, Mice, Mice, SCID, Models, Statistical, Nanotechnology, Neoplasms, therapy, Silicon, Temperature

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          Abstract

          Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.

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          The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting

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            Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy.

            The results obtained in this study establish that liposome formulations incorporating a synthetic polyethylene glycol-derivatized phospholipid have a pronounced effect on liposome tissue distribution and can produce a large increase in the pharmacological efficacy of encapsulated antitumor drugs. This effect is substantially greater than that observed previously with conventional liposomes and is associated with a more than 5-fold prolongation of liposome circulation time in blood, a marked decrease in uptake by tissues such as liver and spleen, and a corresponding increased accumulation in implanted tumors. These and other properties described here have expanded considerably the prospects of liposomes as an effective carrier system for a variety of pharmacologically active macromolecules.
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              Light-absorbing properties, stability, and spectral stabilization of indocyanine green.

              The absorption spectrum of indocyanine green depends on the nature of the solvent medium and on the dye concentration. Binding to plasma proteins causes the principal peaks in the absorption spectrum to shift about 25 nm toward the higher wavelengths. The much greater influence on the spectrum of the dye concentration results from progressive aggregate formation with increasing concentration. Indocyanine green solutions therefore do not follow Lambert-Beer's law above 15 mg-I-1 (in plasma). Indocyanine green solutions in plasma and concentrated (1,000 mg-I-1) solutions in distilled water are stable for at least 4 h. In long-term experiments the optical density of indocyanine green solutions in plasma as well as in distilled water generally diminishes, even in the dark. On the 7th day a new absorption maximum starts to appear at gamma=900 nm, possibly caused by further aggregate formation leading to much larger particles. Spectral stabilization after injection of a concentrated solution into the blood is most rapid when the dye is dissolved in distilled water. Spectral stabilization slows down with decreasing temperature. As rapid spectral stabilization is essential in quantitative dye dilution studies, the practice of adding a albumin and/or isotonic saline solution to the injectate should be discontinued. When a 10 g-1(-1) aqueous solution of indocyanine green is used, spectral stabilization takes less than 1.5 a (at 37 degrees C), which is sufficiently fast for almost any application.
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