LinTT1-Functionalized Hybrid Lipid–Polymer Nanoparticles for Glioblastoma Targeting

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited therapeutic options and a poor prognosis. We developed hybrid lipid-polymer nanoparticles (HLPNs) functionalized with tumor-homing C-end Rule peptide LinTT1 (LinTT1-HLPNs) to improve the GBM targeting. In vitro studies demonstrated that LinTT1-HLPNs bind selectively to GBM cells and significantly improved the cytotoxicity of the loaded temozolomide (TMZ) (LinTT1-HLPNs@TMZ) compared to that of the free drug. In vivo, intravenous injection of HLPNs in both infiltrative and noninfiltrative GBM murine models had an enhanced accumulation of TMZ in the tumor area, thus endorsing the selective targeting and tissue penetration of LinTT1-HLPNs. This nanoplatform combines the advantages of hybrid lipid–polymer nanoparticles with a GBM-specific targeting strategy, thus providing an improved drug delivery and therapeutic effect by a multistep targeting approach, which addresses the key challenge of GBM.