title: Enhanced Antiglioma Efficacy of Ultrahigh Loading Capacity Paclitaxel Prodrug Conjugate Self-Assembled Targeted Nanoparticles.
abstract: Glioblastoma multiforme (GBM) presents one of the most lethal brain tumor with a dismal prognosis. And nanodrug delivery system (nano-DDS) have raised a lot of concern, while the conventional nanoformulations addressed many limitations, especially the low drug loading capacity and poor stability in vivo. Herein, we proposed PTX prodrug (PTX-SS-C18) conjugate self-assembled nanoparticles (PSNPs) functionalized with Pep-1, glioma homing peptide, to overcome the blood brain tumor barrier (BBTB) via interleukin 13 receptor α2 (IL-13Rα2)-mediated endocytosis for targeting GMB. This nanocarrier was with ultrahigh drug loading capacity (56.03%) and redox-sensitivity to the up-expression of glutathione in glioma tumors. And compared with PEG-PSNPs, Pep-PSNPs could significantly enhance cellular uptake in U87MG cells via IL-13Rα2-mediated endocytosis. Enhanced cytotoxicity of Pep-PSNPs against U87MG cells and BCEC cells pretreated with glutathione monoester (GSH-OEt) confirmed that this nanosystem was sensitive to reduction environment, and there was significant difference between targeting and nontargeting groups in MTT assay. Real-time fluorescence image of intracranialU87MG glioma-bearing mice revealed that Pep-PSNPs could more efficiently accumulate at tumor site and improve the penetration. Furthermore, the ex vivo fluorescence imaging and corresponding semiquantitative results displayed that the glioma fluorescence intensity of Pep-PSNPs group was 1.74-fold higher than that of nontargeting group. Pep-PSNPs exhibited remarkable antiglioblastoma efficacy with an extended median survival time. In conclusion, Pep-PSNPs had a promising perspective as a targeting drug delivery system of PTX for glioma treatment.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and §Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and §Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and §Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and §Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and §Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and §Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Mingwan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and §Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Xinrui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and §Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Hongliang
authors.identifier: 0000-0002-2966-7381
authors.initials: H
authors.lastname: Xin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, and §Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D017239:Paclitaxel; D011355:Prodrugs
chemical_list: D011355:Prodrugs; D017239:Paclitaxel
keywords: Paclitaxel; Pep-1 peptide; Prodrug; Redox-responsive; Self-assembled nanoparticles; Targeting