This study demonstrates the capability of multiwalled carbon nanotubes (MWNTs) coupled with laser irradiation to enhance treatment of cancer cells through enhanced and more controlled thermal deposition, increased tumor injury, and diminished heat shock protein (HSP) expression. We also explored the potential promise of MWNTs as drug delivery agents by observing the degree of intracellular uptake of these nanoparticles. To determine the heat generation capability of MWNTs, the absorption spectra and temperature rise during heating were measured. Higher optical absorption was observed for MWNTs in water compared with water alone. For identical laser parameters, MWNT-containing samples produced a significantly greater temperature elevation compared to samples treated with laser alone. Human prostate cancer (PC3) and murine renal carcinoma (RENCA) cells were irradiated with a 1,064-nm laser with an irradiance of 15.3 W/cm2 for 2 heating durations (1.5 and 5 minutes) alone or in combination with MWNT inclusion. Cytotoxicity and HSP expression following laser heating was used to determine the efficacy of laser treatment alone or in combination with MWNTs. No toxicity was observed for MWNTs alone. Inclusion of MWNTs dramatically decreased cell viability and HSP expression when combined with laser irradiation. MWNT cell internalization was measured using fluorescence and transmission electron microscopy following incubation of MWNTs with cells. With increasing incubation duration, a greater number of MWNTs were observed in cellular vacuoles and nuclei. These findings offer an initial proof of concept for the application of MWNTs in cancer therapy.
Previous studies identified various mechanisms of light scattering reduction in tissue induced by chemical agents. Our results suggest that dehydration is an important mechanism of optical clearing in collagenous and cellular tissue. Photographic and optical coherence tomography images indicate that air-immersed skin and tendon specimens become similarly transparent to glycerol-immersed specimens. Transmission electron microscopy images reveal that dehydration causes individual scattering particles such as collagen fibrils and organelles to become more densely packed, but does not significantly alter size. A heuristic particle-interaction model predicts that the scattering particle volume fraction increase can contribute substantially to optical clearing in collagenous and cellular tissue.
Single-walled carbon nanohorns (SWNHs) are new carbonaceous materials. In this paper, we report the first successful preparation of SWNHs encapsulating trimetallic nitride template endohedral metallofullerenes (TNT-EMFs). The resultant materials were functionalized by a highspeed vibration milling method and conjugated with CdSe/ZnS quantum dots (QDs). The successful encapsulation of TNT-EMFs and external functionalization with QDs provide a dual diagnostic platform for in vitro and in vivo biomedical applications of these new carbonaceous materials. Keywords Carbon nanohorns; peapods; quantum dots; in vitro; in vivoCarbon nanomaterials, such as fullerenes and nanotubes, have been studied for decades for their unique properties and various applications. In 1999, Iijima's group reported a new type of carbon nanomaterial, single-walled carbon nanohorns (SWNHs). SWNHs are closed tubules, typically 2-10 nm in diameter and 10-70 nm long, which are composed of single graphitic layers terminating with conical ends.1 , 2 During synthesis, SWNHs form aggregates 40~200 nm in diameter. The size of the aggregates depends on the length of individual SWNHs and can be adjusted by limiting the growth time with an adjustable * Correspondence author: Harry C. Dorn, Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24060; hdorn@vt.edu; Phone: 540-231-5953; Fax: 540-231-3255. NIH Public Access The SWNH peapods were prepared by heating SWNHs at 650 °C in air for 10 minutes to remove amorphous carbon and open windows on the tips and walls. After cooling, TNTEMFs were dissolved in CS 2 and dropped onto the SWNHs. The solvent was evaporated. The mixture of fullerenes and SWNHs was sealed in a quartz tube under 10 −6 Torr. The tube was heated at 470°C for 24 hours. The product was sonicated in toluene for 10 minutes. The solution was filtered through a 0.45 μm polytetrafluoroethylene (PTFE) membrane filter. The solid was washed with toluene until the extract was clear. The TEM samples were prepared by dispersing SWNH peapods in 1, 2-dichloroethane and dropped onto lacey carbon TEM grids.HRTEM images of Lu 3 N@C 80 @SWNHs are shown in Figure 1. In the bright field image ( Figure 1a) at lower magnification fullerene molecules appear to be small circles inside SWNHs. The high angle angular dark field (HAADF) image at higher magnification comfirmed the peapod structue. Due to the significant Z-contrast of HAADF, the Lu atoms appear to be bright spots inside SWNHs (grey area). When the fullerene molecule was at the right orientation, the Lu 3 N cluster appears to be an equilateral triangle as the white circle shows. Similar results were also obtained for NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript mixture was put into a stainless steel capsule and shaken vigorously for 2 hours (SPEX 8000 Mixer/Mill, 1725 rpm). The product was treated with acetone and centrifuged. The supernatant was decanted. The washing procedure was repeated three times to remove excessi...
The significant increases in absorption, temperature elevation, and cell death with inclusion of SWNHs in laser therapy demonstrate the potential of their use as agents for enhancing photothermal tumor destruction.
Background and Objective The complex morphological structure of tissue and associated variations in the indices of refraction of components therein, provides a highly scattering medium for visible and near‐infrared wavelengths of light. Tissue optical clearing permits delivery of light deeper into tissue, potentially improving the capabilities of various light‐based therapeutic techniques, such as adipose tissue removal or reshaping. Study Design/Materials and Methods We report results of a study to evaluate effectiveness of novel mechanical tissue optical clearing devices (TOCD) using white light photography and infrared imaging radiometry (IIR). The TOCD consists of a pin array and vacuum pressure source applied directly to the skin surface. IIR images recorded light absorption and temperature increase of ex vivo porcine skin and adipose during laser irradiation (980 and 1,210 nm) before and after TOCD application. Results White light photographic images of in vivo human skin demonstrated localized compression and altered visual appearance, indicative of water and blood movement in skin. White light photographic images also showed increased visible light transport through regions of ex vivo porcine skin compressed by TOCD pins. Rate of heating in sub‐dermal adipose regions beneath TOCD pins was twofold higher following TOCD application. Conclusions Results of our study suggest that mechanical optical clearing may provide a means to deliver increased light fluence to dermal and adipose tissues. Lasers Surg. Med. 40:688–694, 2008. © 2008 Wiley‐Liss, Inc.
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