A look at nanoshell technology and laser ablation — a new treatment for mast cell disease in canine patients.
Mast cell tumors account for 17.8% of all canine skin tumors diagnosed.1 The majority of these tumors reside in the skin or subcutaneous tissue.2 Overall, breeds with the greatest risk of high grade mast cell tumors are the Shar-Pei, Weimaraner, and Boxer.1 Treatment commonly involves surgical excision, with the goal of obtaining microscopically tumor-free surgical margins.3 Prognosis can be poor and controversial, and depends on the tumor’s location. Certain veterinarians feel that the poor prognosis comes with diagnosis of a poorly-differentiated tumor, whereas others associate it with difficulties in performing surgery.1 Thus, the poor prognosis may be associated with the difficulty of applying an appropriate surgical procedure, and incomplete tumor resection.1 However, a new treatment involving nanoparticles and laser therapy is showing promise for better outcomes.
Nanoparticles and light laser therapy
Laser light therapy (photobiomodulation) with specific light-sensitive dyes has been used for decades to treat specific types of tumor. Nanoparticles, made from noble elements such as gold, are a new discovery, and have an increased sensitivity to visible and near-infrared light absorption as compared to conventional laser phototherapy agents.
The mechanism of action for these new particles, as they enter the body by intravenous administration, is to concentrate in tissue with altered vascular permeability, such as tumor masses. When the nanoparticles are then irradiated with laser light, electrons within them enter an excited state, releasing energy through heat production, and causing an overheating of the regional tissue, along with local cell death and destruction.
Gold nanospheres, nanorods, and nanocages are commonly-used gold nanoparticles, and all have demonstrated an increased ability to absorb visual and near infrared light. The size and shape of the particles allow for vibration and spinning excitation, which produces heat and tissue necrosis when focused laser light is applied to these areas.4
Nanotherapy – pilot study and clinical trials
Companion Animal Health is conducting clinical trials utilizing nanotherapy for several tumor types, and has completed a pilot study with small mast cell tumors. These nanoparticles are made with a gold shell and non-conducting silica core. Their average size is 150 nanometers in diameter. The particles target cancerous tissue, including low grade mast cell tumors due to alterations in the endothelium of the blood supply of these masses, and are then irradiated with focused infrared laser energy.
Initial data from this study was presented at the ACVIM in 2018 and revealed that all patients responded to Companion Nanotherapy, with 67% maintaining remission. The procedure was completed as a single treatment with a very low rate of toxicity (See figures 1-8).5
Currently, more formal study groups are in progress at multiple trial sites, looking at Companion Nanotherapy’s use in oral squamous cell carcinoma (cats), oral and cutaneous melanomas (dogs), and soft tissue sarcomas (dogs). To date, this treatment modality has been used on more than 130 dogs and cats with various types of tumor. All patients have shown a very low rate of toxiciy and complications, thus far.
Given the current treatment options for low-grade cutaneous mast cell tumors, nanoshell therapy and photothermal ablation may offer patients a non-surgical, one-time treatment option with few to no complications. This treatment modality may allow veterinarians to shrink and stop tumor growth in patients that have masses in regions where surgery may not be as successful, and where limited surgical margins may affect prognosis.
1Śmiech A , Ślaska B, Łopuszyński W, Jasik A, Bochyńska, D, Dąbrowski, R. “Epidemiological assessment of the risk of canine mast cell tumors based on the Kiupel two‑grade malignancy classification”. Acta Vet Scand (2018) 60:70.
2Thompson JJ, Pearl DL, Yager JA, Best SJ, Coomber BL, Foster RA. “Canine Subcutaneous Mast Cell Tumor: Characterization and Prognostic Indices”. Veterinary Pathology 48(1) 156-168.
3Milovancev M, Townsend KL, Tuohy JL, et al. “Long-term outcomes of dogs undergoing surgical resection of mast cell tumors and soft tissue sarcomas: A prospective 2-year-long study”. 2019 The American College of Veterinary Surgeons, Veterinary Surgery. 2020;49:96–105.
4Huang X, Jain PK, El-Sayed IH, El-Sayed MA. “Plasmonic photothermal therapy (PPTT) using gold nanoparticles”. Lasers Med Sci (2008) 23:217–228.
5Parshley L. “Nanoparticle and laser thermal ablation in canine low-grade mast cell tumor”. Proceedings, ACVIM Forum, 2018. Olympia Veterinary Cancer Center, Olympia, WA, 2020.