Wei Yanchun, Zhou Feifan, Zhang Da, Chen Qun, Xing Da
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics South China Normal University, Guangzhou 510631, P. R. China.
Nanoscale. 2016 Feb 14;8(6):3530-8. doi: 10.1039/c5nr07785k. Epub 2016 Jan 22.
Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in organic and aqueous environments, respectively. The PPa-NGO-mAb assembly is able to effectively target the αvβ3-positive tumor cells with surface ligand and receptor recognition; once endocytosized by the cells, they are observed escaping from lysosomes and subsequently transferring to the mitochondria. In the mitochondria, the 'on' state PPa-NGO-mAb performs its effective phototoxicity to kill cells. The biological and physical dual selections and on/off control of PPa-NGO-mAb significantly enhance mitochondria-mediated apoptosis of PDT. This smart system offers a potential alternative to drug delivery systems for cancer therapy.
亚细胞器在细胞存活中发挥着关键作用。在这项工作中，基于氧化石墨烯（NGO）作为载体，开发了一种新型光动力疗法（PDT）药物递送及光毒性开关纳米系统，以实现亚细胞靶向和攻击。为构建纳米药物（PPa-NGO-mAb），用整合素αvβ3单克隆抗体（mAb）修饰NGO以实现肿瘤靶向。与聚乙二醇偶联的焦脱镁叶绿酸-a（PPa）用于覆盖NGO表面以诱导光毒性。负载聚乙二醇磷脂以增强水溶性。结果表明，PPa在NGO上的光毒性可分别在有机和水性环境中开启和关闭。PPa-NGO-mAb组装体能够通过表面配体和受体识别有效地靶向αvβ3阳性肿瘤细胞；一旦被细胞内吞，观察到它们从溶酶体中逃逸并随后转移到线粒体。在线粒体中，“开启”状态的PPa-NGO-mAb发挥其有效的光毒性以杀死细胞。PPa-NGO-mAb的生物学和物理双重筛选及开关控制显著增强了光动力疗法中线粒体介导的细胞凋亡。这种智能系统为癌症治疗的药物递送系统提供了一种潜在的替代方案。
