Novel Nano-Drug Delivery System for Brain Tumor Treatment

Abstract

As the most dangerous tumors, brain tumors are usually treated with surgical removal, radiation therapy, and chemotherapy. However, due to the aggressive growth of gliomas and their resistance to conventional chemoradiotherapy, it is difficult to cure brain tumors by conventional means. In addition, the higher dose requirement of chemotherapeutic drugs caused by the blood-brain barrier (BBB) and the untargeted nature of the drug inevitably leads to low efficacy and systemic toxicity of chemotherapy. In recent years, nanodrug carriers have attracted extensive attention because of their superior drug transport capacity and easy-to-control properties. This review systematically summarizes the major strategies of novel nano-drug delivery systems for the treatment of brain tumors in recent years that cross the BBB and enhance brain targeting, and compares the advantages and disadvantages of several strategies.

Keywords: blood–brain barrier; brain tumor; glioma; nano-drug delivery systems.

Figure 1

Schematic of composition and structure of blood–brain barrier and blood–tumor barrier.

Figure 2

Schematic of various mechanisms across the BBB. (a) Adsorption-mediated endocytosis. (b) Water-soluble small molecules pass through the paracellular pathway. (c) Transporter-mediated endocytosis. (d) Receptor-mediated endocytosis. (e) Lipid-soluble small molecules pass through the transcellular pathway. (f) Cell-mediated endocytosis. (g) The tight junction of the BBB at the tumor is destroyed, which can increase the number of small molecules passing through the BBB.

Figure 3

Schematic of strategy of nano drug carrier entering the brain. (a) Cross the BBB by surface modification. (i) Schematic of a nanomedicine carrier modified with ligands targeting receptors. (ii) Schematic of a nanomedicine carrier modified with ligands targeting transporters. (iii) Schematic of a nanomedicine carrier modified with cationic. (b) Biomimetic nano delivery system that can cheat the BBB. (i) Schematic of cells that can pass directly through the BBB, shown here as a neutrophil. (ii) Schematic of drug carrier coated with cell membrane. (iii) Schematic of extracellular vesicle drug delivery system. (iv) Schematic of virus nano drug delivery system. (v) Schematic of protein-based drug delivery system (c) Bypass the BBB by an unconventional route of administration. (i) Schematic of local administration mode, which can be realized by injection or surgical implantation. (ii) Schematic of nose-to-brain administration mode. (d) Schematic of temporary destruction of the blood–brain barrier by ultrasound combined with microbubbles.

Figure 4

Schematic of strategies to enhance brain tumor targeting. (a) Schematic of magnetic targeting brain tumor strategy. (b) Schematic of active targeting strategy, shown here as double targeting strategy.