Dual-targeting of brain tumors with nanovesicles

Abstract

The delivery of chemotherapies to brain tumors faces the difficult task of crossing the blood-brain barrier (BBB).^1-4 The brain capillary endothelial cells (BCECs) along with other cell lines, such as astrocytes and pericytes, form the BBB. This highly selective semipermeable barrier separates the blood from the brain parenchyma. The BBB controls the movement of drug molecules in a selective manner⁵ and maintains central nervous system (CNS) homeostasis. Depending on the properties of drugs such as their hydrophilic-lipophilic balance (HLB), some can cross the BBB through passive diffusion.⁶ However, this approach alone has not led to successful drug developments due to low net diffusion rates and systemic toxicity. Although the use of nanomedicine has been proposed to overcome these drawbacks, many recent studies still rely on the so-called ‘enhanced permeability and retention (EPR)’ effect though there is a realization in the field of drug delivery that EPR effect may not be sufficient for successful drug delivery to brain tumors. Since, compared to many other solid tumors, brain tumors pose additional challenges such as more restrictive blood-tumor barrier as well as the well-developed lymphatic drainage, the selection of functional moieties on the nanocarriers under consideration must be carried out with care to propose better solutions to this challenge.

Keywords: Blood-brain-barrier, Targeted delivery, EPR effect, Lymphatic drainage, Brain tumors, Nanomedicine