Nose-to-Brain Delivery of Cancer-Targeting Paclitaxel-Loaded Nanoparticles Potentiates Antitumor Effects in Malignant Glioblastoma

초록

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 the 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 anticancer effects in vivo. The intranasal (IN) inoculation of RGD-PTX-loaded NPs effectively controls the tumor burden (75 +/- 12% reduction) by inducing apoptosis and/or inhibiting cancer cell proliferation without affecting the G(0) stage of normal brain cells. Our data provide therapeutic evidence supporting the use of intranasally delivered cancer-targeted PTX-loaded NPs for GBM therapy.

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