Engineering of liposomal indocyanine green for photothermally activated combination therapy

Abstract

This dissertation presents drug-loaded liposomal indocyanine green for enhanced combination therapy through thermosensitive release. To accomplish efficient therapeutic effect with reduced side effects, nanobiotechnology has been combined with phototherapy in several decades. Especially, photothermal therapy (PTT) is one of the most efficient therapeutic methods that can induce necrosis of a specific malignant region of tumor with reduced side effects in normal tissues. To realize medical applications of PTT in clinics, near infrared (NIR) region of light has been studied in detail to activate photothermal agent. Indocyanine green(ICG) is the effective NIR fluorescence agent that is FDA approved medical diagnostic agent. Also, ICG has been studied to apply its phototherapeutic effect to treat target disease more efficiently with ICG activation by NIR. However, its physical and chemical characteristics, like albumin binding in bloodstream, fast clearance in human body, solvent-dependent phototherapeutic effect, hinder its therapeutic application, though ICG has unique advantages compared than other phototherapeutic agents. To overcome these problems, ICG-encapsulated nanoparticles have been studied in decades. In this dissertation, liposomal ICG is developed to accomplish photothermal therapy and combination therapy between phototherapy and chemotherapy. The first main research is engineering liposomal indocyanine green (ICG) to maximize its photothermal effects while maintaining the fluorescence intensity. Second main research is enhanced therapeutic efficiency using FDA-approved PTT agent, Indocyanine green (ICG), and drug, cisplatin, and drug carrier, liposomes, by combination therapy through thermosensitive release. Finally, liposomal indocyanine green is applied to selectively treat adipocytes that include excessive lipid droplets to overcome obesity. These results are anticipated to contribute development indocyanine green-based nanoparticles to overcome current problems and to enhance therapeutic efficiency for applying in clinics.