Nanomaterials‐Mediated Structural and Physiological Modulation of Blood Brain Barrier for Therapeutic Purposes

Abstract

Blood brain barrier (BBB) protects homeostasis and sensitive environment of brain from several toxic substances coming from the systemic circulation. This barrier along with those substances also prevents therapeutic chemicals to reach brain tissues for several brain diseases. BBB consists of a number of cell types and junctions that help maintain its intricate structure and physiology. To open BBB for therapeutic purposes, researchers are keen to explore the use of nanomaterials as therapeutic agents. Nanomaterials have unique physio‐chemical properties such as, increased surface area to mass ratio, superior adsorption capacity, and a wide variety of functionalization possibilities in contrast to bulk materials, making them sought‐after for research pertaining to brain delivery of therapeutic substances. Both organic and inorganic nanomaterials have been researched in this regard with numerous interesting functionalizations, and their toxicity and distribution profiles have been well assessed. Different pathways taken up by nanomaterials to cross BBB like adsorptive‐mediated transcytosis, inhibition of active efflux pumps, receptor‐mediated transport, and cell‐mediated endocytosis have also been investigated. This review summarizes the structural and physiological properties and the modulation techniques of BBB for delivery of adsorbed/functionalized nano delivery platforms and imaging nanomaterials across.

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

“…Overall, these studies demonstrate that CDs are a promising NP platform for enhanced BBB permeation through passive diffusion. In addition, lipid-based carriers, such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), can penetrate across the BBB and be translocated in the brain through passive diffusion due to the lipid nature of the BBB , and the nanometric size (40–200 nm) . They are promising lipid-based formulations to treat CNS diseases.…”

“…In addition, lipid-based carriers, such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), can penetrate across the BBB and be translocated in the brain through passive diffusion due to the lipid nature of the BBB 91,92 and the nanometric size (40−200 nm). 93 They are promising lipid-based formulations to treat CNS diseases. SLNs are prepared using solid lipids, such as mono-, di-, and triglycerides, fatty acids, waxes, and steroids.…”

“Block and attack” strategy for tumor therapy through ZnO2/siRNA/NIR‐mediating Zn2+‐overload and amplified oxidative stress

“…Different from ions and small molecules, functional nanomaterials can enter the cell through special ways such as endocytosis, resulting in sudden changes in the distribution of ions and exceed the threshold of self-regulation. [9,10] So far, a variety of ion interference methods, including Ca 2+ , Cl − , Fe 2+ /Fe 3+ and Mn 2+ , have been successfully applied for anti-tumor therapy through combining interference of channel inhibitors and ion donors. [11][12][13][14] Zinc ions (Zn 2+ ) is a key auxiliary component in key metabolic regions of several enzyme molecules involved in protein synthesis, such as ribose nucleic acid (RNA) polymerase.…”

“…Different from ions and small molecules, functional nanomaterials can enter the cell through special ways such as endocytosis, resulting in sudden changes in the distribution of ions and exceed the threshold of self‐regulation. [ 9,10 ]…”