Enhanced Antiglioma Efficacy of Ultrahigh Loading Capacity Paclitaxel Prodrug Conjugate Self-Assembled Targeted Nanoparticles

作者：Yan Jiang, Xiuzhen Wang, Xin Liu, Wei Lv, Hongjuan Zhang, Mingwan Zhang, Xinrui Li, Hongliang Xin, Qunwei Xu · 发表于：ACS Applied Materials & Interfaces · 年份：2016 · DOI：10.1021/acsami.6b13805 · 被引用次数：89 · 研究领域：Nanoplatforms for cancer theranostics、Nanoparticle-Based Drug Delivery、RNA Interference and Gene Delivery

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-C 18 ) 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...