Preparation of Biodegradable Lipid-based Indocyanine Green J-aggregate Nanoparticles for Photothermal Therapy

Abstract

Photothermal therapy (PTT) is an innovative, minimally invasive cancer treatment that utilises light-absorbing agents to convert near-infrared (NIR) light into heat, selectively targeting and destroying cancer cells. The utilisation of a biodegradable (PTT) agent such as indocyanine green J-aggregate (IJA) could potentially address the non-biodegradability issue associated with gold nanoparticles (NPs). Nevertheless, the scalability and development of this agent remain challenging due to several factors, such as the delicate nature of the aggregation, poor optical stabilities in aqueous and biological environments, short in vivo circulation with subsequent dissociation, and the sensitivity to formulation parameters, such as type of solvent, temperature, and surfactants.

This thesis focuses on engineering a multifunctional biodegradable lipid-based system loaded with pre-formed-IJA (p-IJA) as a PTT agent. First, the p-IJA-loaded liposomes were prepared using the lipid film hydration method. The effect of formulation parameters, the physicochemical properties, and thermal activity of the p-IJA-liposomes were studied. It was shown that the processing parameters using rigid lipid (DSPC), cholesterol (50% mol), and PEGylation significantly enhanced p-IJA formation and stability into liposomes with superior heating capacity and nano-size formulation (> 200 nm).

Second, the effect of lipid nanocapsules (LNC) shells on p-IJA formation and stability was investigated. The effect of formulation parameters such as hydrophilic, hydrophobic and cationic surfactants, alongside temperature and particle size were studies. The addition of a hydrophobic surfactant (Span 85) and cationic (DOTAP) to the LNC shell resulted in a stable p-IJA with a higher IJA892/ICG792 ratio.

Finally, solidification of lipid nanoparticle by using solid lipid nanoparticle (SLN) core was explored to improve the IJA892/ICG792 ratio and its heating capacity. Interestingly, higher melting points and solid core lipids such as (sodium stearate) were shown to enhance p-IJA-SLN heating activity through single and multiple heating cycles. This thesis demonstrates the superior heating capacity of p-IJA loaded into a variety of lipid-based systems, enabling its PTT activity.