title: A graphene oxide based smart drug delivery system for tumor mitochondria-targeting photodynamic therapy.
abstract: 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.
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics South China Normal University, Guangzhou 510631, P. R. China. chenqun@scnu.edu.cn xingda@scnu.edu.cn.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Wei
authors.forename: Feifan
authors.initials: F
authors.lastname: Zhou
authors.forename: Da
authors.initials: D
authors.lastname: Zhang
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy*; D006108:Graphite / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010778:Photochemotherapy
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D039302:Integrin alphaVbeta3; D009363:Neoplasm Proteins; D006108:Graphite