Tsuda Takumi, Kaibori Masaki, Hishikawa Hidehiko, Nakatake Richi, Okumura Tadayoshi, Ozeki Eiichi, Hara Isao, Morimoto Yuji, Yoshii Kengo, Kon Masanori
Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.
Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan.
PLoS One. 2017 Aug 31;12(8):e0183527. doi: 10.1371/journal.pone.0183527. eCollection 2017.
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.
已经为肝细胞癌（HCC）患者开发了抗癌药物和手术程序，但其预后仍然很差。有必要开发新的HCC诊断和治疗策略以改善其预后。脂质体是一种核壳型聚合物胶束，将标记物或抗癌药物包裹在这种胶束中可实现药物递送。在本研究中，我们研究了负载吲哚菁绿（ICG）的脂质体用于HCC的近红外荧光（NIF）成像和光动力疗法（PDT）的诊断和治疗效果。
用ICG或ICG-脂质体处理人HCC细胞系HuH-7，然后进行PDT，并测量细胞活力（体外PDT效率）。对于NIF成像，将HuH-7细胞皮下移植到BALB/c裸鼠中，然后静脉注射ICG或ICG-脂质体。对移植后的动物进行PDT治疗，并分析其抗肿瘤作用（体内PDT效率）。
PDT对用ICG-脂质体处理的HuH-7细胞有毒性作用，但对单独的ICG没有毒性作用。NIF成像显示，注射后24小时及之后，ICG-脂质体处理动物的肿瘤区域荧光高于对侧区域。PDT在用ICG-脂质体处理的移植小鼠中产生了即时和持续的光毒性作用。
我们的结果表明ICG-脂质体在异种移植肿瘤中积累，并且PDT对这些恶性植入物具有抗肿瘤作用。ICG-脂质体的NIF成像和PDT可能是HCC有用的诊断和/或治疗策略。
