4 years ago

Self-Assembled Tumor-Penetrating Peptide-Modified Poly(l-γ-glutamylglutamine)–Paclitaxel Nanoparticles Based on Hydrophobic Interaction for the Treatment of Glioblastoma

Self-Assembled Tumor-Penetrating Peptide-Modified Poly(l-γ-glutamylglutamine)–Paclitaxel Nanoparticles Based on Hydrophobic Interaction for the Treatment of Glioblastoma
Ting Peng, Jinge Zhou, Jing Yu, Lei Yu, Yiting Wang, Jing Wang, Shimin Zhao, Weiyue Lu, Lipeng Gao, Lijuan Nan, Lin Zhang, Zhiqiang Yan, Lei Sun, Lin Han
To enhance the tumor-penetrating ability and targeting therapeutic effect of polymer–drug conjugates (PDCs), tumor-penetrating peptide RGERPPR (RGE) modified and PEGylated poly(l-γ-glutamylglutamine)–paclitaxel (PGG–PTX) nanoparticles (RGE–PEG/PGG–PTX NPs) were prepared by using a so-called “modular” design strategy. In brief, a RGERPPR-conjugated targeting material, DSPE–PEG–RGERPPR, was first synthesized and assembled with PGG–PTX into RGE–PEG/PGG–PTX NPs based on the hydrophobic interaction between the groups of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and PTX. The NPs exhibited a uniform spherical morphology with particle size of around 90 nm, as shown by the dynamic light scattering and transmission electron microscopy results. The NPs showed good in vitro stability at 4 °C for over 3 weeks, sustained drug release within 120 h, and good hemocompatibility. The cellular-uptake study displayed that the NPs showed increased uptake by U87 MG cells and human umbilical vein endothelial cells (HUVECs) compared to the unmodified PGG–PTX. The cytotoxicity test demonstrated that RGE–PEG/PGG–PTX NPs produced a stronger growth inhibitory effect against U87 MG cells and HUVECs than PGG–PTX, which was consistent with the cellular uptake results. Finally, the pharmacodynamic study proved that RGE–PEG/PGG–PTX NPs significantly prolonged the median survival time of nude mice bearing intracranial glioblastoma. The results indicated the effectiveness of RGE–PEG/PGG–PTX NPs in the treatment of glioblastoma as well as the feasibility of the “modular” design strategy in the preparation of active-targeting PDCs.

Publisher URL: http://dx.doi.org/10.1021/acs.bioconjchem.7b00519

DOI: 10.1021/acs.bioconjchem.7b00519

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