There is a strong castle defending the brain, the body’s most important organ, inside the maze-like human body. The blood-brain barrier (BBB), a highly selective barrier that controls the flow of chemicals from the bloodstream into the brain, is this guardian. The blood-brain barrier (BBB) is crucial for preserving brain function, but it also makes medication delivery to the central nervous system extremely difficult.
For decades, scientists have grappled with the complexities of breaching this fortress to deliver therapeutics for the treatment of neurological disorders. In recent years, a groundbreaking approach is emerging—one that harnesses the power of nature’s tiniest predators: bacteriophages.
The Phage Frontier: Engineering Nature’s Warriors
Bacteriophages, or simply phages, are viruses that infect and replicate within bacteria, ultimately leading to their destruction. Beyond their role in combating bacterial infections, phages are now being enlisted for a new mission: shuttling drugs across the BBB.
At the forefront of this endeavour is phage display technology—a sophisticated tool that allows scientists to engineer bacteriophages to display specific peptides or proteins on their surface. These engineered phages act as molecular shuttles, capable of targeting and transporting drugs across the BBB.
Cracking the Code: Targeting the BBB
Central to the success of phage-mediated drug delivery is the ability to target the BBB with precision. Scientists have identified various receptors and transport mechanisms on the surface of BBB endothelial cells that can be exploited for targeted drug delivery.
By displaying targeting ligands on their surface, engineered phages can home in on these receptors, facilitating their uptake by BBB endothelial cells—a process known as receptor-mediated transcytosis. This targeted approach ensures that drugs are delivered specifically to the brain, bypassing the systemic circulation and minimizing off-target effects.
The Promise of Precision: Applications in Neuropharmacology
The potential applications of phage-mediated drug delivery across the BBB are vast and far-reaching. From the treatment of brain tumors to neurodegenerative diseases such as Alzheimer’s and Parkinson’s, this innovative approach offers new hope for patients grappling with debilitating neurological disorders.
In the realm of neuro-oncology, phage-mediated drug delivery holds the promise of delivering chemotherapeutic agents directly to brain tumors, sparing healthy surrounding tissue from toxic side effects. In neurodegenerative diseases, such as Alzheimer’s, where the BBB poses a formidable barrier to drug delivery, engineered phages offer a beacon of hope for delivering disease-modifying therapeutics to the brain.
Charting the Course: Navigating Challenges and Opportunities
While the potential of phage-mediated drug delivery across the BBB is undeniable, significant challenges lie ahead. From optimizing phage design and efficacy to ensuring safety and scalability, researchers are faced with a myriad of hurdles on the path to clinical translation.
However, amidst these challenges, there exists an unprecedented opportunity to transform the landscape of neuropharmacology. With continued innovation and collaboration, the promise of phage-mediated drug delivery across the BBB may soon become a reality—a reality where the brain’s fortress is no longer insurmountable, and life-changing therapies reach those in need.
A New Chapter in Neuropharmacology
As we stand at the precipice of a new frontier in neuropharmacology, fueled by the convergence of biotechnology and nature’s design, one thing is clear: the potential of phage-mediated drug delivery across the BBB knows no bounds. With each breakthrough and discovery, we inch closer to a future where neurological disorders are no longer insurmountable obstacles, but challenges to be met with ingenuity, perseverance, and the awe-inspiring power of nature’s tiniest warriors—bacteriophages.
Some of the studies worth reading
Wu, LP., Ahmadvand, D., Su, J. et al. Crossing the blood-brain barrier with nanoligand drug carriers self-assembled from a phage display peptide. Nat Commun 10, 4635 (2019). https://doi.org/10.1038/s41467-019-12554-2
Suárez VM, Vispo NS, Ramos OS. Application of the Phage Display Technology for the Development of Peptide- mediated Drug Delivery Systems through the Blood-Brain Barrier. Curr Pharm Biotechnol. 2021;22(11):1394-1403. doi: 10.2174/1389201022666210104115224. PMID: 33397231.
