Control of optical contrast using gold nanoshells for optical coherence tomography imaging of mouse xenograft tumor model in vivo.

The control of image contrast is essential toward optimizing a contrast enhancement procedure in optical coherence tomography (OCT). In this study, the in vivo control of optical contrast in a mouse tumor model with gold nanoshells as a contrast agent is examined. Gold nanoshells are administered into mice, with the injected dosage and particle surface parameters varied and its concentration in the tumor under each condition is determined using a noninvasive theoretical OCT modeling technique. The results show that too high a concentration of gold nanoshells in the tumor only enhances the OCT signal near the tissue surface, while significantly attenuating the signal deeper into the tissue. With an appropriate dosage, IV delivery of gold nanoshells allows a moderate concentration of 6.2 x 10(9) particles/ml in tumor to achieve a good OCT signal enhancement with minimal signal attenuation with depth. An increase in the IV dosage of gold nanoshells reveals a corresponding nonlinear increase in their tumor concentration, as well as a nonlinear reduction in the fractional concentration of injected gold nanoshells. Furthermore, this fractional concentration is improved with the use of antiepodermal growth factor receptor (EGFR) surface functionalization, which also reduces the time required for tumor delivery from 6 to 2 h.

Concentration dependence of gold nanoshells on the enhancement of optical coherence tomography images: a quantitative study.

The effective use of gold nanoshells as a contrast agent for optical coherence tomography (OCT) may be hampered by the delivery of a wrong dose to tissue that results in unwanted signal attenuation. In this study we examine how changes in mu(s) due to concentration variations affect the OCT image and then define a dosing range that would result in appropriate scattering coefficient, mu(s), to maintain an acceptable signal attenuation level. Our results show that an increase in sample mu(s) not only enhances the OCT signal near the surface but also attenuates the signal deeper into the sample. We synthesized gold nanoshells with an 81 nm radius silica core and 23 nm shell thickness and found that a concentration range of 5.6 x 10(9)

Critical parameters in the pegylation of gold nanoshells for biomedical applications: an in vitro macrophage study.

Pegylation of gold nanoshells provides an effective means to reduce their reticuloendothelial system (RES) clearance in body. In this study, we perform a parametric investigation on the factors that would affect the macrophage uptake of gold nanoshells with the aim to optimize their pegylation and minimize their macrophage uptake. We synthesized and pegylated the gold nanoshells using methoxy-poly(ethylene glycol)-thiol and employed an in vitro macrophage assay to examine the effect of surface density of poly(ethylene glycol) (PEG), chain length of the PEG, and size of the gold nanoshells on their macrophage uptake. We have shown that a saturated surface density would minimize macrophage uptake, which could be obtained by experimental titration-based Ellman's reagent. Our results suggest that the chain length of PEG and size of gold nanoshells influence the surface density of PEG. We have also shown that PEG with molecular weight of around 2000Da and a size range larger than 186nm would be appropriate for facilitating a high surface density. Our in vitro macrophage system thus provides a good model to accurately predict the RES response to different pegylation parameters.

Endoscopic image analysis of photosensitizer fluorescence as a promising noninvasive approach for pathological grading of bladder cancer in situ.

Our aim is to apply image analysis on photosensitizer fluorescence and compare the relationship between histopathology and endoscopic fluorescence imaging. The correlation between hypericin fluorescence and histopathology of diseased tissue was explored in a clinical study involving 58 fluorescence cystoscopic images from 23 patients. Based on quantification of fluorescence colorimetric parameters extracted from the image analysis, diagnostic functions were developed to pathologically classify the bladder cancer. Our preliminary results show that the differences in fluorescence intensity ratios among the three different grades of bladder cancer are statistically significant. The results also show a decrease in macroscopic fluorescence intensity that correlated with higher cancer grades. By combining both the red-to-green and red-to-blue fluorescence intensity ratios into a 2-D scatter plot and defining diagnostic linear discrimination functions on the data points, this technique is able to yield an average sensitivity and specificity of around 68.6% and 86.1%, respectively, for pathological cancer grading of the three different grades of bladder cancer in our study. We conclude that our proposed approach in applying colorimetric intensity ratio analysis on hypericin fluorescence shows potential to optically grade bladder cancer in situ.

Combinatorial treatment of photothermal therapy using gold nanoshells with conventional photodynamic therapy to improve treatment efficacy: an in vitro study.

BACKGROUND AND OBJECTIVE: Both photodynamic (PDT) and photothermal (PTT) therapy have proven to be effective treatment strategies for cancer, but the approach of combining them into a single treatment modality may offer better treatment efficacy. We compare the treatment efficacy of such combined treatment with the individual treatment. STUDY DESIGN/MATERIALS AND METHODS: We perform the individual PDT, PTT and combined treatment under selected in vitro condition with our low light dose of 1.44 J/cm(2) and compare their cell viability using crystal fast violet assay. RESULTS: Compared to PDT and PTT alone which can reduce cell viability to 30.9% and 44.0% respectively, the combined treatment under a single irradiation can further reduce the cell viability to 17.5%. CONCLUSION: A combined PDT and PTT treatment appears to be a more effective treatment strategy compared to conventional PDT or emerging PTT treatment.