Photothermal therapy

Photothermal therapy (PTT) refers to efforts to use electromagnetic radiation (most often in infrared wavelengths) for the treatment of various medical conditions, including cancer. This approach is an extension of photodynamic therapy, in which a photosensitizer is excited with specific band light. This activation brings the sensitizer to an excited state where it then releases vibrational energy (heat), which is what kills the targeted cells.

Unlike photodynamic therapy, photothermal therapy does not require oxygen to interact with the target cells or tissues. Current studies also show that photothermal therapy is able to use longer wavelength light, which is less energetic and therefore less harmful to other cells and tissues.

Most materials of interest currently being investigated for photothermal therapy are on the nanoscale. One of the key reasons behind this is the enhanced permeability and retention effect observed with particles in a certain size range (typically 20 - 300 nm). Molecules in this range have been observed to preferentially accumulate in tumor tissue. When a tumor forms, it requires new blood vessels in order to fuel its growth; these new blood vessels in/near tumors have different properties as compared to regular blood vessels, such as poor lymphatic drainage and a disorganized, leaky vasculature. These factors lead to a significantly higher concentration of certain particles in a tumor as compared to the rest of the body. Coupling this phenomenon with active targeting modalities (e.g., antibodies) has recently been investigated by researchers.

One of the most promising directions in photothermal therapy is the use of gold nanoparticles. Initial efforts with gold nanoparticles, however, were not very effective in vivo because the spherical particles used had peak absorptions limited to 520 to 580 nm for particles ranging from 10 to 100 nm in diameter, respectively. These wavelengths were not effective in vivo because skin, tissues, and hemoglobin have a transmission window from 650 to 900 nm, with peak transmission at approximately 800 nm (known as the Near-Infrared Window). Development of gold nanorods was one solution for the disparity between the wavelengths required to excite spherical gold nanoparticles and the in vivo transmission window. The peak absorption of gold nanorods may be tuned from 550 nm up to 1 micrometre by altering its aspect ratio. Once tuned, the toxic byproducts of CTAB can be removed with non-cytotoxic polyethylene glycol (PEG). PEG not only keeps the nanorods from aggregating in serum once injected, but also increases bloodstream circulation times (leading to better adsorption of nanorods into the cancer tumor). This phenomenon is non-directional (enhanced permeability and retention effect) and has shown to improve tumor accumulation from an intravenous administration (systemic). Several studies report half life circulation times of greater than 15 hours. Once the nanorods have been cleared from the bloodstream, the tumor may be illuminated ex vivo with a diode laser. Nanorods located at distances up to approximately 10 times their diameter absorb roughly 80% of the incident light energy, creating sufficient heat to kill the local (cancer) cells.

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