title: Tumor cells and neovasculature dual targeting delivery for glioblastoma treatment.
abstract: Glioblastoma multiforme (GBM), one of the most common primary malignant brain tumors, was characterized by angiogenesis and tumor cells proliferation. Antiangiogenesis and antitumor combination treatment gained much attention because of the potency in dual inhibition of both the tumor proliferation and the tumor invasion. In this study, a neovasculature and tumor cell dual targeting delivery system was developed through modification of nanoparticles with interleukin-13 peptide and RGD (IRNPs), in which interleukin-13 peptide was targeting GBM cells and RGD was targeting neovasculature. To evaluate the potency in GBM treatment, docetaxel was loaded into IRNPs. In vitro, interleukin-13 peptide and RGD could enhance the corresponding cells (C6 and human umbilical vein endothelial cells) uptake and cytotoxicity. In combination, IRNPs showed high uptake in both cells and increased the cytotoxicity on both cells. In vivo, IRNPs could effectively deliver cargoes to GBM with higher intensity than mono-modified nanoparticles. Correspondingly, docetaxel-IRNPs displayed best anti-tumor effect with a median survival time of 35 days, which was significantly longer than that of mono-modified and unmodified nanoparticles. Importantly, treatment with docetaxel-IRNPs could avoid the accumulation of HIF1α in GBM site, which was crucial for the tumor invasion. After the treatment, there was no obvious change in normal organs of mice.
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education; Department of Pharmaceutics Sciences, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education; Department of Pharmaceutics Sciences, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education; Department of Pharmaceutics Sciences, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Cao
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education; Department of Pharmaceutics Sciences, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education; Department of Pharmaceutics Sciences, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education; Department of Pharmaceutics Sciences, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education; Department of Pharmaceutics Sciences, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: xgjiang@shmu.edu.cn.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009389:Neovascularization, Pathologic
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: Anti-tumor therapy; Antiangiogenesis; Dual targeting delivery; Glioblastoma