title: UPA-sensitive ACPP-conjugated nanoparticles for multi-targeting  therapy of brain glioma.
abstract: Now it is well evidenced that tumor growth is a comprehensive result of multiple pathways, and glioma parenchyma cells and stroma cells are closely associated and mutually compensatory. Therefore, drug delivery strategies targeting both of them simultaneously might obtain more promising therapeutic benefits. In the present study, we developed a multi-targeting drug delivery system modified with uPA-activated cell-penetrating peptide (ACPP) for the treatment of brain glioma (ANP). In vitro experiments demonstrated nanoparticles (NP) decorated with cell-penetrating peptide (CPP) or ACPP could significantly improve nanoparticles uptake by C6 glioma cells and nanoparticles penetration into glioma spheroids as compared with traditional NP and thus enhanced the therapeutic effects of its payload when paclitaxel (PTX) was loaded. In vivo imaging experiment revealed that ANP accumulated more specifically in brain glioma site than NP decorated with or without CPP. Brain slides further showed that ACPP contributed to more nanoparticles accumulation in glioma site, and ANP could co-localize not only with glioma parenchyma cells, but also with stroma cells including neo-vascular cells and tumor associated macrophages. The pharmacodynamics results demonstrated ACPP could significantly improve the therapeutic benefits of nanoparticles by significantly prolonging the survival time of glioma bearing mice. In conclusion, the results suggested that nanoparticles modified with uPA-sensitive ACPP could reach multiple types of cells in glioma tissues and provide a novel strategy for glioma targeted therapy.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Liao
authors.forename: Ting
authors.initials: T
authors.lastname: Jiang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Tuo
authors.forename: Xiaojian
authors.initials: X
authors.lastname: She
authors.forename: Shun
authors.initials: S
authors.lastname: Shen
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D057846:Cell-Penetrating Peptides; D014568:Urokinase-Type Plasminogen Activator; D017239:Paclitaxel