title: PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.
abstract: Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma.
authors: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors: Yan
authors: Y
authors: Jiang
authors: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors: Lingyan
authors: L
authors: Lv
authors: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors: Huihui
authors: H
authors: Shi
authors: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors: Yabing
authors: Y
authors: Hua
authors: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors: Wei
authors: W
authors: Lv
authors: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors: Xiuzhen
authors: X
authors: Wang
authors: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. Electronic address: xhl@njmu.edu.cn.
authors: Hongliang
authors: H
authors: Xin
authors: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. Electronic address: Qunweixu@njmu.edu.cn.
authors: Qunwei
authors: Q
authors: Xu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D003543:Cysteamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D050091:Dendrimers; D053663:Interleukin-13 Receptor alpha2 Subunit; C522249:PEG-PAMAM; C503924:Pep-1 peptide; D010455:Peptides; D011092:Polyethylene Glycols; D003543:Cysteamine
keywords: Glioblastoma; Interleukin 13 receptor α2; Pep-1 peptide; Polyamidoamine dendrimer; Targeted nanocarrier