title: EGFP-EGF1-conjugated nanoparticles for targeting both neovascular and glioma cells in therapy of brain glioma.
abstract: As neovascular and glioma cells were closely associated and might be mutually promoted in glioma growth, a dual-targeting strategy targeting to both neovascular and glioma cells would be more promising as compared with those targeting one of them. In this study, we reported a drug delivery system where nanoparticles were decorated with EGFP-EGF1 (ENP), a fusion protein derived from factor VII with special affinity for tissue factor (TF) over-expressed in glioma tissues, to facilitate anti-glioma delivery of paclitaxel (PTX) by targeting both neovascular and glioma cells. In vitro protein binding assay demonstrated that EGFP-EGF1 bound well to C6 cells and perturbed human umbilical vein endothelial cells (HUVEC) with a concentration-dependent manner but not to unperturbed HUVEC. EGFP-EGF1-TF interaction significantly enhanced nanoparticles uptake by perturbed HUVEC and glioma C6 cells as well as nanoparticles penetration in C6 glioma spheroids, and thus improved the cytotoxicity of their payload in both monolayer cells and glioma spheroids models. In vivo imaging of glioma-bearing mice demonstrated the specific accumulation of ENP in glioma tissues. In vivo distribution of nanoparticles intuitively showed ENP mainly sited in both extravascular glioma cells and neovascular cells. Pharmacodynamic results revealed that PTX-loaded ENP (ENP-PTX) significantly prolonged the median survival time of glioma-bearing mice compared with that of any other group. TUNEL assay and H&E staining showed that ENP-PTX treatment induced significantly more cell apoptosis and tumor necrosis compared with other treatments. In conclusion, the results of this contribution demonstrated the great potential of EGFP-EGF1-functionalized nanoparticles for dual-targeting therapy of brain glioma.
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, PR China.
authors: Bo
authors: B
authors: Zhang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, PR China.
authors: Huafang
authors: H
authors: Wang
authors: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, PR China.
authors: Ziwei
authors: Z
authors: Liao
authors: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, PR China.
authors: Yu
authors: Y
authors: Wang
authors: College of Pharmacy, Jiamusi University, Jiamusi 154007, PR China.
authors: Yue
authors: Y
authors: Hu
authors: College of Pharmacy, Jiamusi University, Jiamusi 154007, PR China.
authors: Jiarong
authors: J
authors: Yang
authors: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, PR China.
authors: Shun
authors: S
authors: Shen
authors: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, PR China.
authors: Jun
authors: J
authors: Chen
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, PR China.
authors: Heng
authors: H
authors: Mei
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, PR China.
authors: Wei
authors: W
authors: Shi
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, PR China. Electronic address: dr_huyu@126.com.
authors: Yu
authors: Y
authors: Hu
authors: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, PR China. Electronic address: zqpang@fudan.edu.cn.
authors: Zhiqing
authors: Z
authors: Pang
authors: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, PR China.
authors: Xinguo
authors: X
authors: Jiang
mesh_terms: D000818:Animals; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000188:drug therapy*; D049452:Green Fluorescent Proteins / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000737:chemistry*
chemical_list: D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017239:Paclitaxel
keywords: Brain glioma; Dual-targeting therapy; EGFP–EGF1; Nanoparticles; Neovascular cells; Tissue factor