光毒性
药物输送
线粒体
聚乙二醇
单克隆抗体
光动力疗法
化学
癌细胞
细胞凋亡
癌症研究
药理学
材料科学
纳米技术
生物化学
体外
癌症
抗体
生物
免疫学
有机化学
遗传学
作者
Yanchun Wei,Feifan Zhou,Da Zhang,Qun Chen,Da Xing
出处
期刊:Nanoscale
[The Royal Society of Chemistry]
日期:2016-01-01
卷期号:8 (6): 3530-3538
被引量:173
摘要
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.
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