Photodynamic therapy is a mode of treatment whereby laser light at a particular wavelength is combined with exogenous chromophores to accomplish therapeutic effect. These exogenous chromophores have often included sensitizers such as protoporphyrin and indocyanine green (ICG) which absorbs the laser energy converting it to heat. [1
]. Photothermal therapy via near infrared (nIR) absorbing nanoparticles has gained great attention and focus in recent years as an improvement to these methods. [4
] The size, shape and chemical structure of gold nanoparticles dictates the optical properties due to interaction of light with the free electrons of the gold surface, a phenomenon referred to as localized surface plasmon resonance, LSPR.
There have been a variety of different types of gold nanoparticles being explored which can be “tuned” to have high absorption characteristics in the nIR region including gold / silica nanoshells, nanorods, and nanocages. [4
] The focus on use of nIR responsive nanoparticles is due to the low absorption and high transmission of light in this wavelength region for the majority of tissue components making it an ideal pairing to use for biomedical applications. [15
] Further, the biocompatibility of gold and ability to conjugate biologically relevant molecules to its surface through the sulfur-gold interaction including polyethylene glycol (PEG) for stealth capabilities and antibodies for targeting make them ideal as therapeutic and diagnostic tools. [4
] Scattering theory, or Mie theory, is an analytical solution to Maxwell’s equation for electromagnetic waves incident on a sphere; using it one can calculate the absorption and scattering cross-section profiles of small particles. [21
] Using simulations based on scattering theory, the optical properties of gold nanoparticles can be predicted based on the type and shape of the particle thus allowing one to design particles with strong light absorption and/or scattering properties at particular wavelengths. [23
Gold nanoparticles with an interior composed of gold sulfide, or gold / gold sulfide composite structures were first produced by self-assembly by Zhou et al.
and shown to have strong nIR absorbing properties. [27
] The optical properties of these materials were later explained to be due to a dielectric core / metal shell structure. [23
] Although some controversy continues over the precise structure of these particles, the core-shell model appears to fit the data well and x-ray diffraction shows a gold surface and gold sulfide composite structure. [28
] Moreover, for work in biomedical application, the particles appear to have a contiguous gold coat which allows for the surface conjugation of molecules as discussed above. Whereas the nIR-resonant gold / silica nanoshells used in therapeutic and imaging applications had an average diameter of 120 – 140 nm, these nIR-absorbing gold / gold sulfide nanoparticles typically have a diameter between 35 – 55 nm. [4
] Using a Mie scattering theory simulation program, we calculated absorbing efficiencies of the gold / gold sulfide nanoparticles to be closer to 96 – 99% based on size measured by transmission electron microscopy (TEM); properties are summarized in . For gold / silica nanoshells used in our previous work with imaging and therapy the particle’s size of 143 nm resulted in a calculated 33% scattering of the light energy or only 67% absorbed for conversion to heat for photothermal therapy. [7
] Previous imaging results were based on use of optical coherence tomography (OCT) via scattering mode detection however, an absorption based mode of OCT detection would likely have to be employed for imaging with the gold / gold sulfide nanoparticles. [31
Properties of gold / gold sulfide nanoparticles compared to gold / silica nanoshells.
Ideally, these smaller particles should provide additional benefits as a cancer therapeutic due to their smaller size, increased absorbing efficiency and ease of manufacture. It is well known that the leaky vasculature of tumors allow extravasation of macromolecules and nanoparticles, allowing therapy based on nanotechnology platforms. [33
] Our postulate in this work is that these gold / gold sulfide nanoparticles will provide additional benefits for treatment of cancer tumors based on their size, allowing better bio-distribution and effective therapeutic benefits for the treatment of fast growing tumors. Modeling work by Decuzzi et al.
suggests that particles with radii less of 50 nm and high relative density (density of a particle relative to the blood) will have a greater ability to move closer to the endothelium layer [36
] potentially enhancing the movement of these particles into the tumors. Further, experimental evidence suggests that nanoparticle uptake into cells is size dependent with the maximum uptake occurring for gold particles of diameters between 30–50 nm. [37