Noninvasive Modulation of the Blood Brain Barrier using PiezoMagnetic Carbon Nanoneedles

ended

Abstract The Blood Brain Barrier (BBB) protects the brain from unwanted chemicals and provides a precisely regulated microenvironment to function normally. However, this defense barrier presents a challenge in shuttling therapeutic cargoes into the brain for the treatment of brain tumours and neurodegenerative diseases. To date, the known methods for BBB penetration poses inherent limitations which are often dangerous to the patients including the microbubble mediated ultrasound (US) driven BBB penetration. Herein we propose an innovative strategy to cross the BBB by introducing PiezoMagnetic Carbon Nanoneedles (PMCNNs) and evaluate its potential as an ideal brain drug delivery system (DDS). PMCNNs are made of functionalised carbon nanotubes (ƒ-CNT) decorated with PiezoMagnetic Nanoparticles. Due to the intrinsic piezoelectric property of PMCNNs, they convert short wave ultrasound (US) into electric pulses to electrically permeate the BBB noninvasively which is not possible by any of the known techniques so far. The main objectives of PiezoMagBBB are 1) to electrically permeate an in vitro BBB model with PMCNNs through nano-electroporation under short wave US and 2) to assess the efficacy of PMCNNs to deliver anticancer therapeutics in 3D tumour spheroids and brain tumour organoids. Thus PiezoMagBBB will design novel PMCNNs; assess their cytotoxicity in different brain cells; evaluate their BBB modulation under US and cellular uptake in BBB models; investigate their potential as a DDS for anticancer drugs in “in vivo tumour mimicking” glioblastoma spheroids and brain-tumour organoids. The fellow brings her extensive expertise in smart DDS design to the host lab, which in turn will offer world-class biological and nanotoxicological facilities and nanomedicine expertise. PiezoMagBBB also offers an industry secondment for high-throughput development of brain tumour organoids and a collaboration with an oncology consultant to enable validation of the model.