TY - JOUR

T1 - Transport of nanomedicines across the blood-brain barrier

T2 - Challenges and opportunities for imaging and therapy

AU - van den Broek, Sara Lopes

AU - Shalgunov, Vladimir

AU - Herth, Matthias M.

N1 - Funding Information: This project has received funding from the European Union 's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813528 .

PY - 2022

Y1 - 2022

N2 - The blood-brain barrier (BBB) is a protective and semipermeable border of endothelial cells that prevents toxins and foreign bodies to enter and damage the brain. Unfortunately, the BBB also hampers the development of pharmaceuticals targeting receptors, enzymes, or other proteins that lie beyond this barrier. Especially large molecules, such as monoclonal antibodies (mAbs) or nanoparticles, are prevented to enter the brain. The limited passage of these molecules partly explains why nanomedicines - targeting brain diseases - have not made it into the clinic to a great extent. As nanomedicines can target a wide range of targets including protein isoforms and oligomers or potentially deliver cytotoxic drugs safely to their targets, a pathway to smuggle nanomedicines into the brain would allow to treat brain diseases that are currently considered ‘undruggable’. In this review, strategies to transport nanomedicines over the BBB will be discussed. Their challenges and opportunities will be highlighted with respect to their use for molecular imaging or therapies. Several strategies have been explored for this thus far. For example, carrier-mediated and receptor-mediated transcytosis (RMT), techniques to disrupt the BBB, nasal drug delivery or administering nanomedicines directly into the brain have been explored. RMT has been the most widely and successfully explored strategy. Recent work on the use of focused ultrasound based BBB opening has shown great promise. For example, successful delivery of mAbs into the brain has been achieved, even in a clinical setting. As nanomedicines bear the potential to treat incurable brain diseases, drug delivery technologies that can deliver nanomedicines into the brain will play an essential role for future treatment options.

AB - The blood-brain barrier (BBB) is a protective and semipermeable border of endothelial cells that prevents toxins and foreign bodies to enter and damage the brain. Unfortunately, the BBB also hampers the development of pharmaceuticals targeting receptors, enzymes, or other proteins that lie beyond this barrier. Especially large molecules, such as monoclonal antibodies (mAbs) or nanoparticles, are prevented to enter the brain. The limited passage of these molecules partly explains why nanomedicines - targeting brain diseases - have not made it into the clinic to a great extent. As nanomedicines can target a wide range of targets including protein isoforms and oligomers or potentially deliver cytotoxic drugs safely to their targets, a pathway to smuggle nanomedicines into the brain would allow to treat brain diseases that are currently considered ‘undruggable’. In this review, strategies to transport nanomedicines over the BBB will be discussed. Their challenges and opportunities will be highlighted with respect to their use for molecular imaging or therapies. Several strategies have been explored for this thus far. For example, carrier-mediated and receptor-mediated transcytosis (RMT), techniques to disrupt the BBB, nasal drug delivery or administering nanomedicines directly into the brain have been explored. RMT has been the most widely and successfully explored strategy. Recent work on the use of focused ultrasound based BBB opening has shown great promise. For example, successful delivery of mAbs into the brain has been achieved, even in a clinical setting. As nanomedicines bear the potential to treat incurable brain diseases, drug delivery technologies that can deliver nanomedicines into the brain will play an essential role for future treatment options.

KW - Active transport

KW - Blood-brain barrier

KW - CNS

KW - Nanomedicines

KW - PET

KW - SPECT

U2 - 10.1016/j.bioadv.2022.213125

DO - 10.1016/j.bioadv.2022.213125

M3 - Review

C2 - 36182833

AN - SCOPUS:85138993405

VL - 141

JO - Biomaterials Advances

JF - Biomaterials Advances

SN - 2772-9508

M1 - 213125

ER -