C-type natriuretic peptide-modified lipid vesicles: fabrication and use for the treatment of brain glioma

// Jia-Shuan Wu 1 , Li-Min Mu 1 , Ying-Zi Bu 1 , Lei Liu 1 , Yan Yan 1 , Ying-Jie Hu 1 , Jing Bai 1 , Jing-Ying Zhang 1 , Weiyue Lu 1 and Wan-Liang Lu 1 1 State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China Correspondence to: Wan-Liang Lu, email: luwl@bjmu.edu.cn Keywords: C-type natriuretic peptide, lipid vesicles, BBB, brain glioma, neovasculatures Received: February 07, 2017     Accepted: March 14, 2017     Published: March 29, 2017 ABSTRACT Chemotherapy of brain glioma faces a major obstacle owing to the inability of drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in brain glioma site result in a rapid infiltration, making complete surgical removal virtually impossible. Herein, we reported a novel kind of C-type natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring drug across the BBB, and for treating brain glioma along with disrupting neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro and on glioma-bearing nude mice in vivo . The results showed that the CNP-modified vinorelbine lipid vesicles could transport vinorelbine across the BBB, kill the brain glioma, and destroy neovasculatures effectively. The above mechanisms could be associated with the following aspects, namely, long circulation in the blood; drug transport across the BBB via natriuretic peptide receptor B (NPRB)-mediated transcytosis; elimination of brain glioma cells and disruption of neovasculatures by targeting uptake and cytotoxic injury. Besides, CNP-modified vinorelbine lipid vesicles could induce apoptosis of the glioma cells. The mechanisms could be related to the activations of caspase 8, caspase 3, p53, and reactive oxygen species (ROS), and inhibition of survivin. Hence, CNP-modified lipid vesicles could be used as a carrier material for treating brain glioma and disabling glioma neovasculatures.