title: Improved anti-glioblastoma efficacy by IL-13Rα2 mediated copolymer nanoparticles loaded with paclitaxel.
abstract: Glioma presents one of the most malignant brain tumors, and the therapeutic effect is often limited due to the existence of brain tumor barrier. Based on interleukin-13 receptor α2 (IL-13Rα2) over-expression on glioma cell, it was demonstrated to be a potential receptor for glioma targeting. In this study, Pep-1-conjugated PEGylated nanoparticles loaded with paclitaxel (Pep-NP-PTX) were developed as a targeting drug delivery system for glioma treatment. The Pep-NP-PTX presented satisfactory size of 95.78 nm with narrow size distribution. Compared with NP-PTX, Pep-NP-PTX exhibited significantly enhanced cellular uptake in C6 cells (p < 0.001). The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively. The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation. Following intravenous administration, Pep-NP-PTX could enhance the distribution of PTX in vivo glioma section, 1.98, 1.91 and 1.53-fold over that of NP-PTX group after 0.5, 1 and 4 h, respectively. Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol(®) (22 days). In conclusion, Pep-NP-PTX is a potential targeting drug delivery system for glioma treatment.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.|Nanjing Drum Tower Hospital. The Affiliated Hospital of Nanjing University Medical School. Nanjing 210008, China.
authors.forename: Baoyan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, 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, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, 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, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000188:drug therapy*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D053663:Interleukin-13 Receptor alpha2 Subunit; D017239:Paclitaxel