Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun, Jilin, 130033, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361005, China.
Biomaterials. 2017 Jan;112:324-335. doi: 10.1016/j.biomaterials.2016.10.030. Epub 2016 Oct 19.
Photodynamic therapy (PDT) is a promising tumor treatment modality that can convert oxygen into cytotoxic singlet oxygen (SO) via photosensitizer to ablate tumor growth. However, the uncontrolled cancer cell proliferation during tumor development and the oxygen consumption during PDT always result in an insufficient oxygen level in tumors, which can adversely affect the PDT efficiency in turn. We designed an oxygen-generating PDT nanocomplex by encapsulating a manganese dioxide nanoparticle (MnO NP) in an indocyanine green (ICG) modified hyaluronic acid nanoparticle (HANP) to overcome this limitation. Because of the excellent fluorescent and photoacoustic properties, the tumor accumulation of the ICG-HANP/MnO (IHM) nanocomplex was monitored by fluorescent imaging and photoacoustic imaging after intravenous administration into the SCC7 tumor-bearing mouse model. Both high fluorescent and photoacoustic signals were detected and found peak at 6 h post-injection (tumor-muscle ratio: 4.03 ± 0.36 for fluorescent imaging and 2.93 ± 0.13 for photoacoustic imaging). In addition, due to the high reactivity of MnO NP to HO, an unfavorable tumor cell metabolic, the oxygen content in the tumor is elevated 2.25 ± 0.07 times compared to that without IHM treatment as ultrasound imaging confirmed. After laser irradiation, significant tumor growth inhibition was observed in the IHM-treated group compared to the ICG-HANP-treated group, attributed to the beneficial oxygen-generating property of IHM for PDT. It is expected that the design of IHM will provide an alternative way of improving clinical PDT efficacy and will be widely applied in cancer theranostics.
光动力疗法（PDT）是一种很有前途的肿瘤治疗方法，它可以通过光敏剂将氧气转化为细胞毒性的单线态氧（SO）来消融肿瘤生长。然而，在肿瘤发展过程中癌细胞的不受控制的增殖和 PDT 过程中的氧气消耗总是导致肿瘤中氧气水平不足，这反过来又会对 PDT 效率产生不利影响。我们设计了一种产氧 PDT 纳米复合物，通过将二氧化锰纳米颗粒（MnO NP）封装在吲哚菁绿（ICG）修饰的透明质酸纳米颗粒（HANP）中，克服了这一限制。由于具有优异的荧光和光声特性，在静脉注射到 SCC7 荷瘤小鼠模型后，通过荧光成像和光声成像监测 ICG-HANP/MnO（IHM）纳米复合物的肿瘤积累。在注射后 6 小时（荧光成像的肿瘤-肌肉比：4.03±0.36，光声成像的肿瘤-肌肉比：2.93±0.13）检测到高荧光和光声信号，并达到峰值。此外，由于 MnO NP 对 HO 的高反应性，这是一种不利于肿瘤细胞代谢的物质，与没有 IHM 治疗相比，肿瘤中的氧气含量升高了 2.25±0.07 倍，这一点通过超声成像得到了证实。激光照射后，与 ICG-HANP 治疗组相比，IHM 治疗组观察到明显的肿瘤生长抑制，这归因于 IHM 对 PDT 的有益产氧特性。预计 IHM 的设计将为提高临床 PDT 疗效提供一种替代方法，并将广泛应用于癌症治疗。
