NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles.
NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles.
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DOI：
10.1039/c4nr03302g
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发表时间：
2014-09
期刊：
影响因子：
6.7
通讯作者：
Youyong Yuan;Yuanzeng Min;Q. Hu;B. Xing;B. Liu
中科院分区：
文献类型：
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作者：
Youyong Yuan;Yuanzeng Min;Q. Hu;B. Xing;B. Liu
具有目标识别和近红外（NIR）激光光调节化学和光动力疗法的纳米平台的设计非常理想，但仍然具有挑战性。在这项工作中，我们利用共轭聚电解质（CPE）-药物共轭物和上转换纳米颗粒（UCNP）开发了这样一个系统。聚乙二醇（PEG）接枝的CPE不仅可以作为UCNP封装的聚合物基质，还可以作为荧光显像剂、光敏剂以及通过紫外可裂解的邻硝基苄基（NB）连接体作为化疗药物阿霉素（DOX）的载体。在 980 nm 激光照射下，UCNP 发出紫外线和可见光。上转换紫外光用于通过邻硝基苯甲基连接体的光裂解来控制药物释放，而上转换可见光用于引发聚合物光敏剂产生用于光动力治疗的活性氧（ROS）。近红外光调节的 UCNP@CPE-DOX 在单次激光照射下在癌细胞中表现出高效率的 ROS 生成和受控药物释放。此外，与单独治疗相比，联合治疗显示出对 U87-MG 细胞生长的增强抑制。由于传统光动力治疗和光调节药物释放总是需要两种不同波长的光源，因此采用UCNP作为近红外光开关非常有利于化疗和光动力联合治疗，增强治疗效果。
The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho-nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects.