Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model

Abstract

Abstract. In this study, the effectiveness and mechanism of combination therapy of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) with simultaneous hyperthermia (HT) on human-derived osteosarcoma in vivo were examined. A tumor model was prepared by subcutaneously implanting human osteosarcoma into nude mice and local injection of ALA was selected as the administration route. This study demonstrated that both ALA-PDT and the combination of ALA-PDT with HT exhibited significant inhibitory effects on tumor growth. In the group with high total energy, the growth inhibition rates of tumor were 52.3% in ALA-PDT, and 27.3% in ALA-PDT with simultaneous HT (PDT+HT), and the synergetic index was 1.76, demonstrating that the inhibitory effect on tumor growth in ALA-PDT was significantly increased by simultaneous use of HT. In the histological findings, after ALA-PDT, necrosis was observed in the area from the surface to a depth of 2 mm, and only a slight effect was confirmed in deeper layers. On the other hand, after PDT+HT, necrosis was observed in layers even deeper than 2 mm below the surface. Furthermore, based on the immunohistochemical findings of the expression of carbonic anhydrase IX, while weak expression of CAIX was observed after ALA-PDT in an area relatively close to the surface, a positive area extended to the deeper layers after PDT+HT compared with ALA-PDT. In conclusion, PDT+HT demonstrated a significant inhibitory effect on tumor growth of human-derived osteosarcoma, and a synergistic interaction of simultaneous HT. This suggests the possibility that ALA-PDT is useful, not only for the treatment of superficial tumors but also for deep-seated mesenchymal tumors, such as osteosarcoma. Furthermore, the mechanism of the synergistic interaction suggested that ALA-PDT was effective in the deep area of tumors due to the increase of blood flow by mild hyperthermia.

In vivoevaluation of battery-operated light-emitting diode-based photodynamic therapy efficacy using tumor volume and biomarker expression as endpoints

“…30 CAIX is a downstream biomarker of hypoxia inducible factor (HIF-1α), upregulated under hypoxic conditions, making CAIX closely associated with hypoxia. [31][32][33] Our observation of high CAIX expression in PDT-treated tumors is consistent with the expectation that photodynamic action would create a hypoxic environment.…”

Antimicrobial photodynamic therapy using visible light plus water-filtered infrared-A (wIRA)

“…Furthermore, it has been shown that wIRA reduces pain in chronic wounds, warts, herpes, scleroderma, gonarthrosis and spondylitis (Fuchs et al, 2004; Hartel et al, 2006). Applying wIRA would enhance the effects of PDT since heating has some synergistic effect when applied together with PDT (Waldow et al, 1985;Kelleher et al, 2003;Yanase et al, 2006). The use of antimicrobial PDT (APDT) could therefore potentially improve the tissue healing process in a number of dental procedures.…”

Photoactivation of 9-hydroxypheophorbide α triggers apoptosis through the reactive oxygen species-mediated mitochondrial pathway and endoplasmic reticulum stress in AMC-HN-3 laryngeal cancer cells

“…Here, we provide additional knowledge concerning its molecular action in cancer cells. Understanding the precise pathways involving the induction of apoptosis may help in the development of treatment modalities of PDT in malignant diseases, either alone or in combination with other therapeutic arms (13,41).…”