Highly reliable, targeted photothermal cancer therapy combined with thermal dosimetry using indocyanine green lactosome

Abstract

Indocyanine green (ICG) is a near-infrared light-absorbing substance. Thus, when a tumor in which ICG has accumulated is irradiated with a near-infrared (NIR) laser, only the tumor can be heated by a photothermal reaction. We developed ICG lactosome, a novel drug delivery system (DDS) composed of polymeric micelles and ICG that shows selective accumulation in tumor based on an enhanced permeability and retention (EPR) effect. We showed that ICG lactosome accumulated in a tumor by using an intradermal tumor mouse model of a murine colon cancer cell line (Colon26) transfected with Nano-lantern luminescent protein (NLC26). Two days after the administration of ICG lactosome, the tumor was irradiated with an 808-nm diode-laser while monitoring tumor temperature. The results showed that the treated tumors were cured when the peak of tumor temperature during NIR irradiation reached 43°C or higher. To verify these results, photothermal therapy (PTT) using ICG lactosome was carried out using a newly developed system that can control the temperature at the NIR irradiation site at a constant level. All of the tumors that had been kept at 43°C during irradiation were cured, while 2 of 5 tumors that had been kept at 42°C were not cured, and none of tumors that had been kept at a temperature below 41°C were cured. ICG 4 lactosome-assisted PTT combined with thermal dosimetry is a highly reliable method for cancer treatment and may afford further clinical opportunities for PTT.

Theranostic Fluorescent Probes

“…Various mechanisms promote the adaptation of tumor cells to this adverse environment and ultimately enhance drug resistance and survival. , PTT is a promising treatment strategy for hypoxic tumors due to its non-oxygen dependence and high spatiotemporal accuracy . PTT uses photothermal agents to trigger local hyperthermia under near-infrared light (NIR) irradiation, with high therapeutic efficiency, leading to irreversible ablation of tumor cells. , To achieve hypoxic reactivity in PTT, hypoxic targeting vectors can be used to deliver photothermal agents or hypoxic-responsive groups can be introduced to activate them. , These strategies are essential for triggering photothermal properties, and the development of novel hypoxia-induced photothermal agents is crucial for controlling the “on/off” state of PTT …”

“… 431 PTT uses photothermal agents to trigger local hyperthermia under near-infrared light (NIR) irradiation, with high therapeutic efficiency, leading to irreversible ablation of tumor cells. 432 , 433 To achieve hypoxic reactivity in PTT, hypoxic targeting vectors can be used to deliver photothermal agents or hypoxic-responsive groups can be introduced to activate them. 434 , 435 These strategies are essential for triggering photothermal properties, and the development of novel hypoxia-induced photothermal agents is crucial for controlling the “on/off” state of PTT.…”

Advances in Nanomaterial-Mediated Photothermal Cancer Therapies: Toward Clinical Applications

“…Indocyanine green (ICG), an FDA-approved medical contrast agent for intravenous administration, has received considerable attention as a phototherapeutic agent given its photothermal effect and cytotoxic ROS generation upon NIR laser irradiation [ 98 , 99 ]. In particular, ICG has been used as an effective NIR-absorbing PTT agent with excellent light-to-heat conversion efficiency for cancer treatment [ 100 , 101 ].…”