Zhuang Xiaoxi, Ma Xiaowei, Xue Xiangdong, Jiang Qiao, Song Linlin, Dai Luru, Zhang Chunqiu, Jin Shubin, Yang Keni, Ding Baoquan, Wang Paul C, Liang Xing-Jie
Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, China.
CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology , Beijing 100190, China.
ACS Nano. 2016 Mar 22;10(3):3486-95. doi: 10.1021/acsnano.5b07671. Epub 2016 Mar 10.
Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.
光动力疗法（PDT）通过在光敏剂和分子氧存在的情况下使用紫外线或可见光来提供一种癌症治疗的替代方法，这可以产生高活性氧物种，最终通过多因素机制导致肿瘤细胞消融。然而，该技术受到入射光穿透深度、实体瘤缺氧环境的限制，并且光漂白的易感性降低了许多成像剂的效率。在这项工作中，我们报道了一种用于高效光动力疗法且具有稳定光反应特性的细胞水平双功能成像和PDT纳米系统——负载咔唑衍生物BMEPC的DNA折纸。咔唑衍生物BMEPC是一种具有大二光子吸收截面的单光子和双光子成像剂及光敏剂，它可以被近红外光完全激发，并且还能够通过产生I型光动力反应的反应中间体在厌氧条件下破坏靶标。然而，BMEPC的应用受到其在水性环境中溶解度差以及聚集导致猝灭的限制。我们观察到负载BMEPC的DNA折纸有效地减少了细胞内BMEPC的光漂白。与DNA折纸结合后，BMEPC的分子内旋转受到适当限制，这在被激发时增强了荧光发射和自由基产生。负载BMEPC的DNA折纸被肿瘤细胞摄取后，在照射时，BMEPC会产生自由基，并由于DNA光裂解以及随后的部分降解而释放。然后自由基的产生诱导细胞凋亡。这种功能纳米系统为设计用于有效细胞内成像和光动力疗法的负载光敏剂的DNA折纸提供了思路。
