Chlorin e6 Derivative Radachlorin Mainly Accumulates in Mitochondria, Lysosome and Endoplasmic Reticulum and Shows High Affinity toward Tumors in Nude Mice in Photodynamic Therapy

• Published in: Photochemistry and photobiology 2014-09, Vol.90 (5), p.1108-1118
• Main Authors: Biswas, Raktim, Moon, Jeong Hwan, Ahn, Jin-Chul
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Biological Transport; Cancer; Drug Combinations; Endoplasmic Reticulum - metabolism; Female; Light; Lysosomes - metabolism; Medical treatment; Mice; Mice, Nude; Mitochondria; Mitochondria - metabolism; Neoplasm Transplantation; Photochemotherapy; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - pharmacology; Porphyrins - pharmacokinetics; Porphyrins - pharmacology; Thyroid Carcinoma, Anaplastic - drug therapy; Thyroid Carcinoma, Anaplastic - metabolism; Thyroid Carcinoma, Anaplastic - pathology; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Tissue Distribution; Tissues; Toxicity; Tumor Burden - drug effects; Tumor Burden - radiation effects
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.12273

The efficacy of photodynamic therapy (PDT) depends upon the amount of photosensitizer accumulated in the malignant tissues. Radachlorin is a popular photosensitizer used in photodynamic therapy to treat various types of cancer. In this study, we have studied the main organelles responsible for the accumulation of radachlorin in human anaplastic thyroid cancer in vitro and in vivo. The optimal time window for uptake and clearance of radachlorin also was studied. Confocal microscopic images confirmed that the radachlorin is mainly acquired by mitochondria and partially by lysosome and endoplasmic reticulum. Studies also showed that the maximum amount of radachlorin was accumulated within 3–6 h after the treatment. Radachlorin also showed a higher affinity toward malignant tumors compared to the other organs in mice xenograft model. Uptake of radachlorin reached an optimum amount within 6 h and most of the radachlorins were also cleared from the body in next 48 h. Therefore, detailed information regarding exact accumulation sites and a time window in which maximum amount of drug is accumulated and cleared were obtained by this study. Hence, not only the efficacy of the treatment can be increased but the phototoxicity after the treatment also can be controlled. Cellular uptake and tumor affinity of chlorin e6 photosensitizer, radachlorin were studied in anaplastic thyroid cancer cells and xenograft nude mice model. Results showed radachlorin mainly accumulated in mitochondria and partially in lysosome and endoplasmic reticulum. It showed a higher accumulation in tumor site within 3–6 h and was further cleared from the tumor in next 24–48 h. Radachlorin also showed a higher efficacy in photodynamic therapy after 6 h of drug injection. Therefore, the knowledge of possible sites and time of photosensitizers accumulation in tumor cells may help in optimizing the efficacy of PDT.