Monocytic delivery of therapeutic oxygen bubbles for dual-modality treatment of tumor hypoxia
Monocytic delivery of therapeutic oxygen bubbles for dual-modality treatment of tumor hypoxia
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DOI：
10.1016/j.jconrel.2015.09.016
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发表时间：
2015-12-28
影响因子：
10.8
通讯作者：
Chiu, Hsin-Cheng
中科院分区：
文献类型：
--
作者：
Huang, Wen-Chia;Shen, Ming-Yin;Chiu, Hsin-Cheng
光动力学疗法（PDT）是一种强有力的光化学技术，用于激活恶性细胞的凋亡。尽管PDT在几种临床应用中显示出前景，但由于治疗剂的运输限制和PDT的氧依赖性，缺氧区域中的恶性细胞通常对PDT具有抗性。在此，我们提出了一种创新的策略，克服PDT在肿瘤缺氧的限制，使用骨髓来源的单核细胞作为细胞的车辆共同运输的氧气和红光激活的光敏剂，二氢卟酚e6（Ce 6）。制备了超顺磁性氧化铁纳米颗粒/Ce 6/载氧聚合物气泡，并内化到肿瘤单核细胞中。发现这些功能性气泡在没有外部触发的情况下对细胞宿主无害。然而，在用高频磁场和红光激光（660 nm）治疗肿瘤时，治疗性单核细胞在抑制Tramp-C1荷瘤小鼠（C57 BL/6 J）的肿瘤生长方面表现出上级性能。肿瘤切片的组织学检查证实了治疗有效载荷向肿瘤缺氧的成功细胞转运以及由联合热疗/光动力疗法沿着额外的氧气供应引起的显著抗肿瘤作用。这项工作表明，这种通过肿瘤嗜性单核细胞向肿瘤缺氧的氧/治疗剂共递送有希望改善PDT疗效。(C)2015爱思唯尔B. V.保留所有权利。
Photodynamic therapy (PDT) is a powerful technique photochemically tailored for activating apoptosis of malignant cells. Although PDT has shown promise in several clinical applications, malignant cells in hypoxic regions are often resistant to PDT due to the transport limitation of therapeutics and the oxygen-dependent nature of PDT. Herein, we present an innovative strategy for overcoming the limits of PDT in tumor hypoxia using bone marrow-derived monocytes as cellular vehicles for co-transport of oxygen and red light activatable photosensitizer, chlorin e6 (Ce6). Superparamagnetic iron oxide nanoparticle/Ce6/oxygen-loaded polymer bubbles were prepared and internalized into tumortropic monocytes. These functional bubbles were found harmless to cellular hosts without external triggers. Nevertheless, the therapeutic monocytes exhibited a superior performance in inhibiting tumor growth on Tramp-C1 tumor-bearing mice (C57BL/6J) upon the treatments of tumors with high frequency magnetic field and red light laser (660 nm). Histological examinations of the tumor sections confirmed the successful cellular transport of therapeutic payloads to tumor hypoxia and the pronounced antitumor effect elicited by combined hyperthermia/photodynamic therapy along with the additional oxygen supply. This work demonstrates that this oxygen/therapeutic co-delivery via tumortropic monocytes toward tumor hypoxia is promising for improving PDT efficacy. (C) 2015 Elsevier B.V. All rights reserved.