Free and nanoencapsulated indocyanine green for near infrared and multiphoton bioimaging

Abstract

Early-stage cancer detection is a crucial step towards successful cancer treatment as well as for improving the patient survival rate. In recent years, molecular imaging has gained tremendous interest in early-stage cancer diagnosis. Nowadays, for molecular imaging scientific community has started to use the exogenous contrast agents to improve the detection ability of the existing imaging modalities. Especially, the use of exogenous near-infrared fluorescence (NIRF) contrast agents has improved the quality of NIR optical bioimaging. It helps in visualization of deeply buried inhomogeneities inside the tissue due to less scattering, low endogenous absorption, and almost zero auto-fluorescence in the NIR wavelength range. Additionally, it enables researchers to study the deep-seated abnormalities with an enhanced signal-to-noise ratio (SNR). Indocyanine green (ICG) is the only U. S. Food and Drug Administration (FDA) approved NIRF dye that is being used in clinics for the last approximately 60 years. However, the use of ICG to the fullest has been limited due to its short blood circulation time, non-specific binding within the body, undesirable aggregation, poor aqueous stability, poor cellular uptake, and poor optical and thermal stability. These limitations of the ICG could be addressed by the nanoencapsulation of ICG within a carrier for site-specific delivery. To date, various nanocarriers have been developed, such as micelles, liposomes, polymers, metals, and composites, etc. However, none of them has reached clinical practice due to limitations such as non-biodegradability and non-biocompatibility, which leads to short and long-term cellular toxicity. Keeping these limitations in mind, the primary focus of this thesis has been to encapsulate ICG within biocompatible and biodegradable nanocarriers. A green chemistry-based two-step self-assembly method has been developed to fabricate these nanoparticles. The ICG loaded nanoparticles demonstrated an improved efficiency of ICG delivery in cells in comparison with the free form of ICG.