Editorial Feature

"Nanoswimmers" to Carry Drugs Through Blood Brain Barrier

Researchers at the University College London’s Department of Chemistry have recently developed a method to carry drugs to the blood brain barrier using chemotactic movement. Chemotaxis, also known as chemotactic movement, is the movement of cells or organism in response to chemical movement. The chemotactic movement is facilitated and driven by the chemical environment present around it, and the concentration gradient determines the direction of this movement.

Adrian Joseph and his team utilized this principle to propel tiny vesicle nanoswimmers, known as polymerosomes, which are tiny vesicles filled with chemicals, to transport drugs into the blood brain barrier. When these polymerosomes sense glucose, they self-propel towards the higher concentration regions from the lower concentration regions by inducing slip velocity on their surface. Because this movement is based on the concentration gradient, it is an extremely sensitive process.

The brain, which is the center of the nervous system in vertebrates and invertebrates, has a protective barrier that is responsible for the precise control of substances entering and leaving the brain, otherwise known as the “blood brain barrier.” Unlike the endothelial cells present in other organs, the brain endothelial cells form continuous tight junctions between them, thereby limiting the diffusion of molecules across the membrane1.

While water channels present in the astrocytic foot processes allow water to enter, the transport of other molecules, such as glucose and essential amino acids, require secondary transport systems1.

Although the blood brain barrier helps protect individuals from the influence of some endogenous hormones and harmful chemicals, certain drugs such as drugs to treat brain ailments need to enter the brain to show their desired pharmacologic activity2. Despite the extensive research on providing drugs access to the brain, it remains a significant challenge for certain drugs to cross the blood brain barrier.

Adrian Joseph’s team at the University College London have created a fully synthetic, organic nanoscopic system based on the chemotactic movement driven by the enzymatic conversion of glucose. Within the human body, glucose oxidase is an enzyme that converts endogenous glucose to D-glucono-lactone and water, and along with it a harmful byproduct, hydrogen peroxide (H2O2) ,which is then converted into water and oxygen by another enzyme known as catalase2.

Glucose oxidase is encapsulated into nanoscopic and asymmetric polymer vesicles known as “polymerosomes” that are formed by self-assembly of amphiphilic copolymers in water. Catalases that convert hydrogen peroxide to water and oxygen were included along with glucose oxidase in one kind of polymerosomes, whereas the other kind consisted of just the glucose oxidase2. These vesicles offer great advantages over liposomes, which are naturally occurring phospholipid molecules, in terms of their physicochemical properties and ability to load large amounts of biomolecules, such as proteins and nucleic acids.

By using two different copolymers, either poly[(2-methacryloyl) ethyl phosphorylcholine]–poly[2-(diisopropylamino) ethyl methacrylate] (PMPC-PDPA) or poly[oligo(ethylene glycol) methyl methacrylate] (POEGMA)–PDPA along with poly(ethylene oxide) poly(butylene oxide) (PEO-PBO) copolymers, this group of Researchers were able to obtain vesicles with lateral segregation resulting in the asymmetric polymerosomes which have greater permeability on one side as compared to the rest of the vesicle2.

The active diffusion studies showed that both the asymmetric polymers (PMPC-PDPA/PEO-PBO) polymerosomes loaded with glucose oxidase alone and glucose oxidase with catalases showed chemotactic movement based on the glucose gradient, whereas the symmetric polymers (PMPC-PDPA) loaded polymerosomes with glucose oxidase and catalase did not show any such chemotactic movement2. Furthermore, this group of Researchers also used biologically inert POEGMA polymerosomes to demonstrate that the asymmetric polymerosomes used here could target specific cells by loading low density lipoprotein receptor protein-1 (LRP-1) targeting peptide, “Angiopep-2” into the polymerosomes.

The results revealed that the Angiopep-2 loaded polymerosomes facilitated a four-fold increase in penetration to the brain compared to the non-chemotactic systems suggesting that POEGMA polymerosomes have the potential to cross the blood brain barrier and enter the CNS2.

This research proposes a novel mechanism where polymerosomes that utilizes the chemotaxis mechanism to race up the concentration gradient to cross the blood brain barrier and enter an area of higher glucose concentration. Because of the capability of these polymerosomes to load biomolecules, as demonstrated by the loading of Angiopep-2 here, polymerosomes in the future have the potential to cross the blood brain barrier to deliver important drugs to the brain.

Image Credit:

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  1. “Blood-brain Barrier Maintains the Constancy of the Brain’s Internal Environment” – University of Texas Health Science Center at Houston
  2. “Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing” A. Joseph, C. Contini, et al. Science Advances. (2017). DOI: 10.1126/sciadv.1700362.

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Benedette Cuffari

Written by

Benedette Cuffari

After completing her Bachelor of Science in Toxicology with two minors in Spanish and Chemistry in 2016, Benedette continued her studies to complete her Master of Science in Toxicology in May of 2018. During graduate school, Benedette investigated the dermatotoxicity of mechlorethamine and bendamustine, which are two nitrogen mustard alkylating agents that are currently used in anticancer therapy.


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