Near-Infrared Light Triggered ROS-activated Theranostic Platform based on Ce6-CPT-UCNPs for Simultaneous Fluorescence Imaging and Chemo-Photodynamic Combined Therapy.
Near-Infrared Light Triggered ROS-activated Theranostic Platform based on Ce6-CPT-UCNPs for Simultaneous Fluorescence Imaging and Chemo-Photodynamic Combined Therapy.
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作者：
Yue C;Zhang C;Alfranca G;Yang Y;Jiang X;Yang Y;Pan F;de la Fuente JM;Cui D
许多药物控制释放方法已经集成到多功能纳米颗粒中，例如pH-、氧化还原-、温度-、酶-和光响应释放。然而，很少有报道与活性氧反应的药物控制释放。本文制备了一种基于硫代缩酮接头的活性氧响应药物（与硫代缩酮接头缀合的喜树碱，缩写为TL-CPT），并且硫代缩酮接头可以被活性氧（活性氧）切割。为了实现肿瘤的同步光学成像、光动力学治疗和化疗，将光敏剂二氢卟酚e6（Ce 6）、TL-CPT和羧基-mPEG负载到上转换纳米粒子（UCNPs）上，制备了Ce 6-CPT-UCNPs。在980 nm激光照射下，Ce 6-CPT-UCNPs在645-675 nm处有一个窄的发射带，与Ce 6的吸收峰重叠。Ce 6吸收光以产生ROS，其用于光动力学疗法并切割Ce 6-CPT-UCNP中的硫代缩酮接头以释放用于化疗的喜树碱。同时，Ce 6吸收了光，用于近红外荧光成像。体内生物分布研究表明，制备的纳米粒具有较高的原位肺癌靶向效率。体内治疗结果表明，NCI-H460肺癌可以通过联合化疗和980 nm激光照射下的光动力学治疗完全消除。所制备的多功能Ce 6-CPT-UCNPs在肿瘤靶向荧光成像、活性氧激活的化学和光动力治疗等方面具有巨大的应用潜力。
Many drug controlled release methods have been integrated in multifunctional nanoparticles, such as pH-, redox-, temperature-, enzyme-, and light-responsive release. However, few report is associated with the ROS responsive drug controlled release. Herein, a thioketal linker-based ROS responsive drug (camptothecin conjugated with thioketal linker, abbreviated as TL-CPT) was prepared and the thioketal linker could be cleaved by ROS(reactive oxygen species). To achieve cancer simultaneous optical imaging, photodynamic therapy and chemotherapy, the photosensitizer Chlorin e6(Ce6), TL-CPT and carboxyl-mPEG were loaded on the upconversion nanoparticles (UCNPs), which were named as Ce6-CPT-UCNPs. Under 980 nm laser irradiation, Ce6-CPT-UCNPs emitted a narrow emission band at 645-675 nm which was overlapped with Ce6 absorption peak. Ce6 absorbed the light to produce ROS, which was used for photodynamic therapy and to cleave the thioketal linker in Ce6-CPT-UCNPs to release camptothecin for chemotherapy. Meanwhile, Ce6 absorbed the light, was used for near-infrared fluorescence imaging. The in vivo biodistribution studies showed that the prepared nanoparticles had high orthotopic lung cancer targeting efficiency. The in vivo therapeutic results demonstrated that NCI-H460 lung cancers could be completely eliminated by combining chemo- and photodynamic therapy under 980 nm laser irradiation. The prepared multifunctional Ce6-CPT-UCNPs have great potential in applications such as cancer targeted fluorescent imaging, simultaneous ROS activated chemo- and photodynamic therapy in near future.