Abstract

ABSTRACTNovel methods are needed to traverse the blood-brain barrier and deliver drugs to specific targets in the brain. To this end, MS2 bacteriophage was explored as a multifunctional transport and targeting vector. The MS2 capsid exterior was modified with two different targeting moieties for delivery across the BBB and targeting specific regions of interest in the brain. Successful modification of MS2 capsids with a brain targeting peptide and NMADAR2D-targeting antibody was confirmed by immunoblotting and fluorescence detection. To measure transport efficiency of MS2 particles across an in vitro BBB model, a highly sensitive RT-qPCR protocol was developed and implemented. Finally, in order to demonstrate the potential of MS2 as a drug delivery vehicle, nucleotide-mediated loading of capsids was investigated with the MRI contrast agent Gd-DOTA modified with psoralen.

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