Synergistic effect of photothermal and photoimmunological reactions in treatment of metastatic tumors

Abstract

The use of several different drugs and different treatment modalities often leads to synergistic effects in treating diseases, such as cocktail therapy in AIDS treatment and combination therapy in chemotherapy treatment of cancer patients. With the wide application of lasers in the treatment of cancers, can the synergistic effect manifest itself in the combination application of lasers and other treatment components, particularly those related to immunological stimulation? Selective photothermal interactions using a laser and a light-absorbing dye have been used in combination with immunological interactions using an in situ immunoadjuvant in treating metastatic tumors. Three components were used in this method: a near-infrared laser, a light-absorbing dye and an immunoadjuvant. This new method -- Laser Immunotherapy -- has achieved the synergistic effect. This novel approach has been applied in treating metastatic mammary tumors in rats. In our animal studies, when the components were applied individually, or in two-component combinations, the long-term effect of cancer treatment was almost negligible. However, when the three components were used at the same time, the treatment effect improved significantly. In this study, we show the synergistic effect using an 805~nm laser, indocyanine green (ICG) as the light-absorbing dye, and glycated chitosan, a novel compound, as the immunostimulant. Furthermore, optimization of the laser-dye photothermal interaction using different laser and dye parameters in an in vitro study using tissue-simulating gel phantoms was performed. Our results showed that the optimal photothermal effect could be achieved using 1.8 watts and 0.5~cm beam radius, and an ICG concentration between 0.08 to 0.14% effect of immunoadjuvant, three additional adjuvants, complete Freund's adjuvant, incomplete Freund's adjuvant, and C-parvum were also used in laser immunotherapy. Glycated chitosan appeared to be the most effective. The complete Freund's adjuvant at a dose of 200 μl and 50% concentration resulted in a cure rate comparable to that using glycated chitosan. Incomplete Freund's adjuvant and C-parvum showed relative weak effects in treating the metastatic tumors.