Nose-to-Brain Delivery of Cancer-Targeting Paclitaxel-loaded Nanoparticles Potentiates Anti-Tumor Effects in Malignant Glioblastoma

Glioblastoma multiforme (GBM) is an aggressive tumor with no curative treatment. The tumor recurrence after resection often requires chemotherapy or radiation to delay the infiltration of tumor remnants. Intracerebral chemotherapies are preferentially being used to prevent tumor regrowth, but treatments remain unsuccessful because of poor drug distribution in the brain. In this study, we investigated the therapeutic efficacy of cancer-targeting arginyl-glycyl-aspartic tripeptide (RGD) conjugated paclitaxel (PTX)-loaded nanoparticles (NPs) against GBM by nose-to-brain delivery. Our results demonstrated that RGD-modified PTX-loaded NPs showed cancer-specific delivery and enhanced anti-cancer effects in vivo. The intranasal (IN) inoculation of RGD-PTX-loaded NPs effectively control the tumor burden (75±12% reduction) by inducing apoptosis and/or inhibiting cancer cell proliferation without affecting the G0 stage of normal brain cells. Our data provide therapeutic evidence supporting the use of intranasally d...