Abstract
The blood–brain barrier (BBB) is formed by brain microvascular endothelial cells that are sealed by tight junctions, making it a significant obstacle for most brain therapeutics. The poor BBB penetration of newly developed therapeutics has therefore played a major role in limiting their clinical success. A particularly challenging therapeutic target is glioma, which is the most frequently occurring malignant brain tumor. Thus, to enhance therapeutic uptake in tumors, researchers have been developing strategies to modulate BBB permeability. However, most conventional BBB opening strategies are difficult to apply in the clinical setting due to their broad, non-specific modulation of the BBB, which can result in damage to normal brain tissue. In this review, we have summarized strategies that could potentially be used to selectively and efficiently modulate the tumor BBB for more effective glioma treatment.
Highlights
Gliomas are one of the more frequent tumors occurring in the central nervous systems (CNS), accounting for over 32% of primary CNS cancers and over 77% of primary malignant brain cancers [1]
The BBB is formed by brain microvascular endothelial cells (BMECs) that work in concert with other cells of the neurovascular unit such as pericytes, astrocytes and neurons to regulate the movement of molecules and cells between blood and brain (Figure 1A)
The findings suggest that use of oral nitric oxide (NO) donors may be a strategy to enhance the delivery of chemotherapeutics to malignant brain tumors [100]
Summary
Gliomas are one of the more frequent tumors occurring in the central nervous systems (CNS), accounting for over 32% of primary CNS cancers and over 77% of primary malignant brain cancers [1]. A variety of strategies have been suggested to overcome the tumor BBB, improving drug delivery in treating glioma [16] These include approaches to increase drug permeability through chemical modification, inhibition of efflux transporters, transcytosis via targeting of endogenous BBB transporters/receptors, and osmotic BBB disruption, among others and these have been reviewed elsewhere [16,17,18]. Such strategies can often lead to broad drug distribution in the brain, which can result in damage to the non-diseased tissue. We will discuss drug delivery strategies that hinge on selective targeting of pathological tumor BBB disruption or selective biochemical or physical modulation of tumor BBB permeability to allow for enhanced, localized drug uptake to glioma
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