Near-infrared light triggered drug delivery system for higher efficacy of combined chemo-photothermal treatment
Near-infrared light triggered drug delivery system for higher efficacy of combined chemo-photothermal treatment
复制标题
近红外光触发药物输送系统可提高化学光热联合治疗的疗效
DOI：
10.1016/j.actbio.2016.12.004
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发表时间：
2017-03-15
影响因子：
9.7
通讯作者：
Ci, Tianyuan
中科院分区：
文献类型：
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作者：
Chen, Yi;Li, Haohuan;Ci, Tianyuan
化疗和光热疗法的结合是一种很有前途的癌症治疗策略。在本研究中，吲哚菁绿色（ICG），一种广泛使用的近红外（NIR）染料在光热治疗，和化疗药物阿霉素（DOX）内的新设计的芳基硼酸酯和胆固醇修饰的透明质酸（PPE-Choli-HA）的纳米粒子，表示为PCH-DI。我们利用ICG产生活性氧的能力和芳基硼酸酯对活性氧的敏感性来实现药物的可控释放。结果表明，PCH-DI具有明显的光热效应，并能在近红外激光照射下光触发DOX的快速释放。PCH-DI/Laser组中的DOX在体外表现出对HCT-116结肠细胞的最有效的核结合。在近红外激光照射下，PCH-DI对HCT-116肿瘤裸鼠移植瘤和AOM诱导的小鼠原位结直肠癌模型的细胞毒作用增强，肿瘤生长抑制作用增强。因此，基于PCH的共递送系统似乎是一个很有前途的平台，联合化疗光热治疗在肿瘤治疗中的Statement of Significance在化疗光热联合治疗的情况下，治疗的同步性在实现预期的抗肿瘤效率中起着重要的作用。本研究利用活性氧敏感的芳基硼酸酯和活性氧产生剂ICG，构建了一种光触发活性氧介导的药物传递系统。我们创新性地利用了ICG在NIR激光照射下的ROS产生能力，以促进由于芳基硼酸酯的存在而导致的PCH-DI溶胀导致的DOX的更快释放。细胞内活性氧检测结果表明，照射后PCH-I细胞内活性氧水平升高。此外，通过体外药物释放和细胞摄取研究证实了近红外激光照射下PCH-DI中DOX的快速释放行为。同时，通过光热效应实验验证了局部热疗的有效性。因此，通过光触发的DOX的更快释放（化疗）和在照射下使用PCH-DI的局部热疗（热疗法）来实现组合疗法的同步。PCH-DI在体内外的有效抗肿瘤效果归因于化疗-光热联合治疗的协同效应，实现了同步化。为此，这种新型的共递送系统为实现治疗的同步性以加强联合治疗的效率提供了有前途的解决方案。(c)2016由Elsevier Ltd代表Acta Materialia Inc.发布。
The combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. In the present study, indocyanine green (ICG), a widely used near-infrared (NIR) dye in photothermal therapy, and chemotherapeutic drug-doxorubicin (DOX) were loaded within the nanoparticles of novel designed arylboronic ester and cholesterol modified hyaluronic acid (PPE-Choli-HA), denoted as PCH-DI. We take advantage of reactive oxygen species (ROS) production capability of ICG and ROSsensitivity of arylboronic ester to realize controllable drug release. It was confirmed that PCH-DI exhibited remarkable photothermal effect and light-triggered faster release of DOX with NIR laser irradiation. DOX in PCH-DI/Laser group exhibited the most efficient nucleus binding toward HCT-116 colon cells in vitro. Furthermore, enhanced cytotoxicity and promoted tumor growth suppression effect of PCH-DI on HCT-116 tumor xenograft nude mice and AOM-induced murine orthotopic colorectal cancer model was achieved under NIR laser irradiation. Thus, the co-delivery system based on PCH appears to be a promising platform for the combined chemo-photothermal therapy in tumor treatment.Statement of SignificanceIn case of chemo-photothermal combination therapy, the synchronism of treatments plays an important role in achieving expected antitumor efficiency. In this study, a light triggered ROS mediated drug delivery system was developed with the help of ROS-sensitive moieties of arylboronic ester and ROS producer of ICG. We innovatively make use of the ROS production capability of ICG under NIR laser irradiation to promote a faster release of DOX resulting from swelling of PCH-DI due to the presence of arylboronic ester. Intracellular ROS detection demonstrated that ROS level of PCH-I increased under irradiation. Moreover, the faster release behavior of DOX from PCH-DI with NIR laser irradiation was confirmed by the in vitro drug release and cellular uptake study. Meanwhile, local hyperthermia was verified by photothermal effect tests. Therefore, the synchronism of the combination therapy was achieved via light triggered faster release of DOX (chemo-therapy) and local hyperthermia (thermal-therapy) using PCH-DI under irradiation. It was reasonable to attribute the efficient anti-tumor efficiency of PCH-DI both in vitro and in vivo to the enhanced synergistic effect of chemo-photothermal combination therapy with realization of synchronism. To this end, this novel co-delivery system has provided a promising solution for achieving the synchronism of treatment to strengthen the efficiency of combination therapy. (c) 2016 Published by Elsevier Ltd on behalf of Acta Materialia Inc.