Engineering nanoparticle-assembled capsules for near-infrared phototherapy
Wong, Michael S.
Doctor of Philosophy
Phototherapy is a non-intensive, selective, and simple method for treating diseases such as cancer. It has fewer side effects and can be more affordable than traditional treatments. There is a great interest in near-infrared light (NIR) because this radiation can penetrate deeper into biological tissue at a wide range of wavelengths. Indocyanine green (ICG) is a photosensitizer that absorbs and fluoresces in NIR range, and thus has been used for clinical imaging and diagnostics for more than 20 years. ICG has been found useful in light-based treatment through the generation of singlet oxygen or heat. However, ICG binds non-specifically to plasma proteins, has a short residence time in the blood stream, and has poor thermal stability and photo stability in aqueous solution. Encapsulation of ICG is a useful approach to address these limitations. The objectives of this research were to understand the mechanism of nanoparticle (NP) assembly and to apply it in ICG encapsulation. This simple procedure involves combining solutions of poly(allylamine hydrochloride) (PAH) and phosphate ions, adding an ICG solution, and finally, adding a silica nanoparticle(NP) sol. ICG was encapsulated into PAH/phosphate/silica capsules with loadings up to 23 wt%, much higher than other reported materials. The encapsulated ICG was found to have similar photothermal heating capabilities as the unencapsulated ICG. Silica NPs were replaced successfully by epidermal growth factor receptor (EGFR) antibody biomolecules, which could be regarded as biological NPs. The binding specificity of these antibody-displayed ICG-containing capsules was tested in cancer cells. Cell specificity and photothermal effect were demonstrated using 1483 cells and NIR irradiation (808 nm). Finally, the introduction of magnetic functionality was explored by replacing silica NPs with Fe3 O4 NPs. Magnetic response can potentially enhance delivery efficiency due to the influence of an external magnetic field. The capsules were found to noticeably change the ICG biodistribution in white female mice via intravenous injection. ICG was found to accumulate more in lungs when ICG was encapsulated. 2% increase of ICG percentage (as capsules) in the blood was observed at 2.5 min in the presence of an external magnetic field (0.03 Tesla) placed under the mouse tail where the ICG-capsules were injected.