[SELECTIVE PHOTOTHERMOLYSIS]

Laser therapeutics has long been thought of as an alternative to physical tumor resection.  The idea is that a laser could be used to destroy undesired tissue growth as observed in tumors.  In theory, the procedure is relatively simple to perform and has the potential to be less invasive.  Also, the ability to treat embedded tumors in vital regions lacking surgical access is attractive.  Selective photothermolysis is an optical technique used to ablate tissue in targeted regions.  The major goal of the technique is to heat targeted tissue with a laser and destroy it without damaging surrounding tissue.  Targeted cells are damaged mainly through the absorption of light in a desired region and the subsequent heating of tissue due to energy transfer.  Heating of the tissue denatures proteins and halts major cell survival processes.  However, the major limitation to the process is selectivity - it must be able to only damage the desired tumor.  Simply heating the tissue would not be enough since there is no way to control the diffusion of heat.  This can result in catastrophic damage to healthy surrounding tissue.^[4]

The issue of selectivity has been tackled by a combination of a couple of factors.  First and foremost, laser parameters have been a tool do increase selectivity.  Decreasing pulse times in lasers have allowed surgeons to provide short burst of energy to tissue.  This short pulse time creates enough power to heat the local target and limit peripheral damage.  However, it's short exposure time is significantly less than the thermal conductivity time of the tissue.  As a consequence, there is minimal thermal diffusion outside of the site of laser exposure.  However, some of these short pulsed lasers can prove to be expensive and also is limited by the ability to target the laser accurately.    In addition, there has been work involving using photosensitizers.  In this case, a highly absorbing dye is used as a way to selectively absorb the laser light.  These dyes, such as indocyanine green, can be used as highly absorbing agents in a tumor.  The particles in the dye absorb most of the laser light and thus cause the greatest thermal increase in the region.  However, these dyes can be fairly transient  due to photobleaching effects when applied in laser therapeutics.  As a result, the window of opportunity to effectively benefit from the dye is short.  Thus, a more stable and longer-lasting substitute as a photosensitizer is desirable.^[4]

Given their properties, gold nanoparticles are an attractive photosensitizer choice.  Specifically, in the case of nanoshells, they are optically tunable to the near infrared region - the most viable laser wavelength choice and also provide a more stable and reliable option to current dyes.  Nanoshells can convert light to heat with far more efficiency that dyes.  In addition, nanoshells can be manufactured such that they can selectively accumulate in tumors.  It has been shown that the leaky vasculature of tumors encourages small particles (60-400nm) to accumulate.  This effect is referred to as the "enhanced permeability of retention".  Tumor vasculature tends to possess wide interendothelial junctions, an incomplete basement membrane,  a dysfunctional lymphatic system and a large number of transendothelial channels.  All of these are factors that support nanoparticle accumulation.  Additionally, specific antibodies can be attached to nanoshells to enhance selectivity.^[4]