The Effects of Ultrasound and Light on Indocyanine‐Green‐Treated Tumour Cells and Tissues

Abstract

Photodynamic therapy (PDT) is emerging as a treatment modality for the management of neoplastic disease. Despite considerable clinical success, its application for the treatment of deep-seated lesions is constrained by the inability of visible light to penetrate deeply into tissues. An emerging alternative approach exploits the fact that many photosensitisers respond to ultrasound, eliciting cytotoxic effects on target cells and tissues; this has become known as sonodynamic therapy (SDT). The objectives of this study were 1) to determine whether the IR-absorbing dye, indocyanine green (ICG), can be employed as a sonosensitiser and 2) to determine whether ultrasound can be used to enhance ICG-mediated PDT. Exposing ICG-treated mouse fibrosarcoma cells to ultrasound at an energy density of 30 J cm(-2) decreased cell viability by 65 %. Prior exposure of ICG-treated cells to light (λ 830 nm) and subsequent treatment with ultrasound led to a 90 % decrease in cell viability. In combination treatments a synergistic effect was observed at lower doses of ultrasound. Microscopic examination of cell populations treated with light or ultrasound demonstrated the production of intracellular reactive oxygen species (ROS). Using a mouse tumour model, treatment with light, ultrasound, or a combination thereof led to respective decreases in tumour growth of 42, 67, and 98 % at day 27 post-treatment. These results could provide a means of circumventing light-penetration issues that currently challenge the widespread use of PDT in the treatment of cancer.

Effect of Hematoporphyrin Monomethyl Ether-Sonodynamic Therapy (HMME-SDT) on Hypertrophic Scarring

“…Hypertrophic scars not only affect the appearance and functions of skin, but also can result in psychological burdens for the patient. They are unique to humans and occur in response to surgery, trauma, burns, or other forms of dermal injury and inflammatory conditions, and do not regress spontaneously[2]. Clinically, they are characterized by massive scar formation, which invades normal adjacent skin and extends beyond the region of the initial wound.…”

“…In the present study, SDT, also named sonodynamic chemistry therapy (SDCT) [2] was used to treat hypertrophic scars on the surface of rabbit ears. On the basis of our previous studies, we combined the application of hematoporphyrin monomethyl ether (HMME) with SDT to explore the potential for synergistic treatment efficacy upon hypertrophic scars in rabbit ears.…”

Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

“…[22][23][24] Studies have demonstrated that ICG can be activated by both light and ultrasound. 25 However, the applications of ICG are mainly hindered by some characteristics, including instability (aqueous instability, thermal degradation, and photodegradation), high protein binding (which leads to its rapid elimination from the body), lack of targeting, and its proneness to photobleaching. [26][27][28] An investigation of the new nanotechnology and drug delivery systems would bring hope to overcome these restrictions.…”

Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy

“…These effects include the photo-and sonosensitizing activity of ICG, as well as the induction of PCI of chemotherapeutic agents on the basis of the amphiphilic nature of the molecule. In our own studies, we have demonstrated the cytotoxic and antitumour effect of intratumorally-injected ICG, in combination with laser light and low-intensity ultrasound [21]. The photo-and sonosensitizing effects of ICG, triggered by light and ultrasound irradiation, have been attributed to mitochondrial destruction that leads to the build-up of intracellular cytotoxic free radicals and subsequent cell death.…”