Abstract
Metronomic photodynamic therapy (mPDT) is a form of PDT that induces cancer cell death by intermittent continuous irradiation with a relatively weak power of light for a long duration (several days). We previously developed a wirelessly powered, fully implantable LED device and reported a significant anti-tumor effect of mPDT. Considering application in clinical practice, the method used for repeated administrations of photosensitizers required for mPDT should not have a high patient burden such as the burden of transvenous administration. Therefore, in this study, we selected 5-aminolevulinic acid (ALA), which can be administered orally, as a photosensitizer, and we studied the antitumor effects of mPDT. In mice with intradermal tumors that were orally administered ALA (200 mg/kg daily for 5 days), the tumor in each mouse was simultaneously irradiated (8 h/day for 5 days) using a wirelessly powered implantable green LED device (532 nm, 0.05 mW). Tumor growth in the mPDT-treated mice was suppressed by about half compared to that in untreated mice. The results showed that mPDT using the wirelessly powered implantable LED device exerted an antitumor effect even with the use of orally administered ALA, and this treatment scheme can reduce the burden of photosensitizer administration for a patient.
Highlights
One of the effective cancer treatments is photodynamic therapy (PDT)
After administration to the body, aminolevulinic acid (ALA) is transferred into cells and is metabolized into protoporphyrin IX (PPIX), which functions as a photosensitizer
To determine the amount of ALA required to exert an antitumor effect in Metronomic photodynamic therapy (mPDT), we investigated the relationship between ALA dose and the amount of PPIX produced
Summary
One of the effective cancer treatments is photodynamic therapy (PDT). PDT uses a photosensitizer and light in well-oxygenated cancer tissue to generate reactive oxygen species (ROS), resulting in cancer cell d eath[1]. Tumorselective treatment is possible when light can be directed only to the tumor, and PDT spares patients from many of the adverse effects associated with chemotherapy, radiation, and surgery[2]. Conventional PDT requires a light source that is capable of delivering about 100 mW/cm[2] of irradiation intensity, whereas mPDT only requires a low intensity of about 0.1 mW/cm[2], making it possible to reduce the size of the light source This may allow implantation of the light source inside the body and treatment of tumors in deeply located organs in body cavities (cranial, thoracic, and abdominal cavities), which has not been possible with conventional PDT. Considering the need for repeated administrations, ALA is the most desirable photosensitizer among the currently available photosensitizers
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