Functionalization and Characterization of an MRI-Capable, Targeted Nanoparticle Platform for Delivery to the Brain
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MRS Advances © 2018 Materials Research Society DOI: 10.1557/adv.2018.357
Functionalization and Characterization of an MRICapable, Targeted Nanoparticle Platform for Delivery to the Brain S. M. Curley, J. Castracane, M. Bergkvist, N. C. Cady SUNY Polytechnic Institute, Colleges of Nanoscale Sci. & Eng. Albany, NY
ABSTRACT
Novel 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.
INTRODUCTION Delivery of imaging agents and pharmaceutical payloads to the central nervous system (CNS) is essential for efficient diagnosis and treatment of brain diseases. Therapeutic delivery, however, is often restricted by the blood-brain barrier (BBB). Gadolinium-based contrast agents have been used extensively for brain imaging of strokes and tumors, as these pathological conditions compromise the BBB, allowing imaging agents access to brain tissue for image enhancement. When the BBB is intact, contrast agents are unable to enter the brain due to their hydrophilicity. Thus a multifunctional drug delivery system is needed that: 1) can be loaded with functional molecules, 2) transport across the BBB, and 3) localize to specific regions in the brain for image enhancement and potential diagnosis of currently undetectable brain pathologies. One highly versatile platform that has yet to be used specifically for brain targeting and transport is the MS2 bacteriophage. MS2 is a well-studied, 28 nm virus that has recently emerged as a potential drug delivery vehicle [1, 2]. The MS2 viral capsid is comprised of 180 coat proteins that can be chemically modified through 540 available lysine residues on the capsid exterior surface. Additionally, the MS2 capsid contains 32 pores with diameters ranging from 1.6-1.8 nm, with an interior void volume of approximately 7 nm in diameter containing single-stranded RNA, making it possible to load the capsid with imaging agents or drugs via nucleotide-mediated interactions [3].
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This study provides a detailed description of MS2 capsid modification for brain ta
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