Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy.
Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy.
复制标题
具有充足氧气供应的自我监测人造红细胞，用于增强光动力治疗
DOI：
10.1038/srep23393
复制
发表时间：
2016-03-18
影响因子：
4.6
通讯作者：
Cai L
中科院分区：
文献类型：
--
作者：
Luo Z;Zheng M;Zhao P;Chen Z;Siu F;Gong P;Gao G;Sheng Z;Zheng C;Ma Y;Cai L
光动力疗法已越来越多地应用于临床癌症的治疗。然而，自然缺氧的肿瘤微环境和缺乏氧气供应是阻碍光动力学反应的主要障碍。为了解决这个问题，我们开发了仿生人工红细胞，通过负载氧载体(血红蛋白)和光敏剂(吲哚青绿)的络合物来增强光动力学策略。这种纳米系统提供了稳定的自供氧耦合结构，作为理想的荧光/光声成像探针，动态监测纳米粒子的生物分布和PDT的治疗。当受到近红外激光照射时，远程触发的光敏剂会产生大量的细胞毒性活性氧物种(ROS)，并提供充足的氧气供应。重要的是，血红蛋白同时被氧化成更活跃和更稳定的铁基血红蛋白，从而导致持久的细胞毒性。ROS和铁基血红蛋白协同触发异种移植瘤的氧化损伤，导致完全抑制。具有自我监测和增强光动力效应的人造红细胞可以作为一个多功能的治疗平台。
Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.