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: Baoyan Wang, Lingyan Lv, Zhi Wang, Yan Jiang, Wei Lv, Xin Liu, Zhongyuan Wang, Yue Zhao, Hongliang Xin, Qunwei Xu
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 16589 (Nov 16 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26567528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Drug Carriers
• Interleukin-13 Receptor alpha2 Subunit
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics)
• Brain (metabolism)
• Brain Neoplasms (drug therapy)
• Cell Line, Tumor
• Drug Carriers (administration & dosage, pharmacokinetics)
• Glioblastoma (drug therapy)
• Interleukin-13 Receptor alpha2 Subunit (metabolism)
• Male
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Mice, Nude
• Nanoparticles (administration & dosage)
• Paclitaxel (administration & dosage, pharmacokinetics)
• Rats
• Tissue Distribution
• Xenograft Model Antitumor Assays