基于氧化石墨烯量子点上转换纳米晶杂化纳米粒子的协同靶向和高效光动力疗法,Small

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基于氧化石墨烯量子点上转换纳米晶杂化纳米粒子的协同靶向和高效光动力疗法
Small ( IF 13.0 ) Pub Date : 2018-04-17 , DOI: 10.1002/smll.201800293
Yan Liu ₁ , Yawen Xu ₂ , Xiangshuai Geng ₃ , Yingying Huo ₂ , Dexin Chen ₁ , Kang Sun ₁ , Guangdong Zhou ₂ , Biqiong Chen ₄ , Ke Tao ₁

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在基于纳米粒子的光动力疗法（PDT）和其他纳米疗法中，将纳米疗法定位在活性部位，尤其是在亚细胞范围内非常重要。然而，尽管纳米制剂在活性细胞器上的积累导致更好的治疗效果，但亚细胞靶向剂通常是非特异性的。本文通过使用具有丰富官能团的氧化石墨烯量子点（GOQD）作为双重靶向修饰的载体和产生活性氧的光敏剂，以及上转换纳米粒子（UCNs）作为激发光的换能器来设计PDT纳米配方。肿瘤靶向剂叶酸和线粒体靶向部分羧丁基三苯基phosph，通过表面修饰将它们同时附着在UCNs-GOQDs杂化纳米颗粒上，并且根据体外和体内实验，这些纳米颗粒均获得了协同靶向作用。与没有或只有一个靶向部分的UCNs-GOQDs纳米颗粒的结果相比，观察到更显着的细胞死亡和更大程度的线粒体损伤。此外，PDT对荷瘤小鼠的功效也得到了有效改善。总的来说，当前的工作提出了一种协同策略，以增强亚细胞靶向和PDT在癌症治疗中的功效，这也可能为其他种类的纳米疗法提供启示。与没有或只有一个靶向部分的UCNs-GOQDs纳米颗粒的结果相比，观察到更显着的细胞死亡和更大程度的线粒体损伤。此外，PDT对荷瘤小鼠的功效也得到了有效改善。总的来说，当前的工作提出了一种协同策略，以增强亚细胞靶向和PDT在癌症治疗中的功效，这也可能为其他种类的纳米疗法提供启示。与没有或只有一个靶向部分的UCNs-GOQDs纳米颗粒的结果相比，观察到更显着的细胞死亡和更大程度的线粒体损伤。此外，PDT对荷瘤小鼠的功效也得到了有效改善。总的来说，当前的工作提出了一种协同策略，以增强亚细胞靶向和PDT在癌症治疗中的功效，这也可能为其他种类的纳米疗法提供启示。

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Synergistic Targeting and Efficient Photodynamic Therapy Based on Graphene Oxide Quantum Dot‐Upconversion Nanocrystal Hybrid Nanoparticles

Locating nanotherapeutics at the active sites, especially in the subcellular scale, is of great importance for nanoparticle‐based photodynamic therapy (PDT) and other nanotherapies. However, subcellular targeting agents are generally nonspecific, despite the fact that the accumulation of a nanoformulation at active organelles leads to better therapeutic efficacy. A PDT nanoformulation is herein designed by using graphene oxide quantum dots (GOQDs) with rich functional groups as both the supporter for dual targeting modification and the photosensitizer for generating reactive oxygen species, and upconversion nanoparticles (UCNs) as the transducer of excitation light. A tumor‐targeting agent, folic acid, and a mitochondrion‐targeting moiety, carboxybutyl triphenylphosphonium, are simultaneously attached onto the UCNs–GOQDs hybrid nanoparticles by surface modification, and a synergistic targeting effect is obtained for these nanoparticles according to both in vitro and in vivo experiments. More significant cell death and a higher extent of mitochondrion damage are observed compared to the results of UCNs–GOQDs nanoparticles with no or just one targeting moiety. Furthermore, the PDT efficacy on tumor‐bearing mice is also effectively improved. Overall, the current work presents a synergistic strategy to enhance subcellular targeting and the PDT efficacy for cancer therapy, which may also shed light on other kinds of nanotherapies.

更新日期：2018-04-17

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