Near-infrared fluorescence imaging and photodynamic therapy with indocyanine green lactosome has antineoplastic effects for hepatocellular carcinoma

• Published in: PloS one 2017-08, Vol.12 (8), p.e0183527
• Main Authors: Tsuda, Takumi, Kaibori, Masaki, Hishikawa, Hidehiko, Nakatake, Richi, Okumura, Tadayoshi, Ozeki, Eiichi, Hara, Isao, Morimoto, Yuji, Yoshii, Kengo, Kon, Masanori
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antineoplastic agents; Antitumor agents; Apoptosis; Biocompatibility; Biology and Life Sciences; Bladder cancer; Breast cancer; Cancer therapies; Carcinoma, Hepatocellular - diagnostic imaging; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - therapy; Care and treatment; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - radiation effects; Diagnostic systems; Dosage and administration; Drug delivery; Drug delivery systems; Engineering and Technology; Esophagus; Fluorescence; Gastric cancer; Health aspects; Hepatocellular carcinoma; Humans; I.R. radiation; In vitro methods and tests; Indocyanine Green - administration & dosage; Infrared imaging; Intravenous administration; Laboratories; Lasers; Light; Liver cancer; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - pathology; Liver Neoplasms - therapy; Lymphatic system; Medical diagnosis; Medical prognosis; Medicine and Health Sciences; Metastasis; Mice; Nanoparticles; Optical Imaging; Photochemotherapy; Photodynamic therapy; Prognosis; Research and Analysis Methods; Stomach cancer; Surgery; Surgical implants; Toxicity; Tumors; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0183527

Anticancer agents and operating procedures have been developed for hepatocellular carcinoma (HCC) patients, but their prognosis remains poor. It is necessary to develop novel diagnostic and therapeutic strategies for HCC to improve its prognosis. Lactosome is a core-shell-type polymeric micelle, and enclosing labeling or anticancer agents into this micelle enables drug delivery. In this study, we investigated the diagnostic and therapeutic efficacies of indocyanine green (ICG)-loaded lactosome for near-infrared fluorescence (NIF) imaging and photodynamic therapy (PDT) for HCC. The human HCC cell line HuH-7 was treated with ICG or ICG-lactosome, followed by PDT, and the cell viabilities were measured (in vitro PDT efficiency). For NIF imaging, HuH-7 cells were subcutaneously transplanted into BALB/c nude mice, followed by intravenous administration of ICG or ICG-lactosome. The transplanted animals were treated with PDT, and the antineoplastic effects were analyzed (in vivo PDT efficiency). PDT had toxic effects on HuH-7 cells treated with ICG-lactosome, but not ICG alone. NIF imaging revealed that the fluorescence of tumor areas in ICG-lactosome-treated animals was higher than that of contralateral regions at 24 h after injection and thereafter. PDT exerted immediate and continuous phototoxic effects in the transplanted mice treated with ICG-lactosome. Our results demonstrate that ICG-lactosome accumulated in xenograft tumors, and that PDT had antineoplastic effects on these malignant implants. NIF imaging and PDT with ICG-lactosome could be useful diagnostic and/or therapeutic strategies for HCC.