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.
Highlights
Brain glioma is a type of tumor that originates in the brain [1, 2]
The results showed that the C-type natriuretic peptide (CNP)-modified vinorelbine lipid vesicles could transport vinorelbine across the blood-brain barrier (BBB), kill the brain glioma, and destroy neovasculatures effectively
To synthesize the CNP-TPGS1000 conjugate, TPGS1000 was reacted with glutaric acid to form COOHTPGS1000
Summary
Brain glioma is a type of tumor that originates in the brain [1, 2]. Brain glioma cells infiltrate rapidly and disrupt the architecture of brain tissue, making complete resection virtually impossible [3]. Malignant brain glioma can rarely be cured by surgery or radiotherapy alone [4]. Chemotherapy is used to clear tumor cells. Treatment with anticancer drugs is hindered by the blood–brain barrier (BBB), which hinders the intravenously administered anticancer agents entering the region of brain glioma [5, 6]. The neovasculatures of brain glioma cannot be removed readily by resection, and angiogenesis further facilitates the growth of brain glioma [9, 10]
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