Abstract 817: Effective near infrared laser-induced photothermal therapy for cancer using indocyanine green/methyl-Β-cyclodextrin compound loaded liposomal nanoparticle

Abstract

Abstract Background: Photothermal therapy (PTT) is a promising cancer therapeutic process to eliminate solid cancer through thermal ablation using electromagnetic radiation and photothermal agent (PTA). PTT is efficient in treating tumor because tumor has a lower heat resistance due to the shortage of blood supply. Also, it has less invasiveness, low toxicity to normal tissues, high spatial specificity, and minimal drug resistance. Indocyanine green (ICG), an FDA approved agent, is a widely used as a PTA and imaging probe in clinical application. However, ICG has several major shortcomings that may hinder its practical use such as short half-life in circulatory system, unspecific binding to protein, and rapid decomposition by heat, light and aqueous solution, resulting in a decrease in PTT efficacy. To overcome these problems, we developed ICG/methyl-beta-cyclodextrin (MB-CD) compound-loaded liposomal nanoparticle by host-guest complexation between ICG and MB-CD and its liposome formation. It was possible to improve ICG stability and anti-tumor efficacy. Method: Liposomes were synthesized using 1,2-Distearoyl-sn-glycero-3-phosphoethanolamone-N-(methoxy-(polyethylene glycol)-5000), 1,2-Distearoyl-sn-glycero-3-phosphocholine, cholesterol, methanol, and chloroform by film hydration method. To form ICG/MB-CD compound (IDC), ICG and MB-CD solution were mixed and purified. Then it was loaded into liposomal nanoparticles and filtered to prepare ICG/MB-CD compound-loaded liposome (IDL). Results: We compared ICG, IDC, indocyanine green loaded liposome (ICL), and IDL. IDC and IDL were characterized by absorbance spectra, fluorescence spectrometer, dynamic light scattering, and transmission electron microscopy. IDL was less decomposed in various solvents than others, indicating of higher in vitro stability. Moreover, IDL had an enhanced fluorescence intensity among the four groups due to the protection of ICG conjugated structure by MB-CD. In addition, it was remarkable for IDL to be the least bleached by near infrared laser compared to others for demonstrating its better photothermal stability and retention ability. In confocal imaging and in vitro PTT experiment using 4T1 breast cancer cell line, IDL was well uptaken by the cells and showed the highest cancer therapeutic efficacy. Furthermore, in vivo and ex vivo fluorescence imaging were performed using 4T1 tumor bearing mice after intravenous injection of the particles. As a result, IDL injected group demonstrated the highest tumor uptake among the four groups. Conclusions: IDL was successfully synthesized and exhibited excellent optical property, stability, and anti-tumor efficacy. Thus, it could be a promising PTA for treatment of solid cancer. Citation Format: MinKyu Kim, Hyung-Jun Im. Effective near infrared laser-induced photothermal therapy for cancer using indocyanine green/methyl-Β-cyclodextrin compound loaded liposomal nanoparticle [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 817.