Functionalised Carbon Nanotubes Enhance Brain Delivery of Amyloid-Targeting Pittsburgh Compound B (PiB)-Derived Ligands

Costa, Pedro Miguel; Wang, Julie Tzu-Wen; Morfin, Jean-François; Khanum, Tamanna; To, Wan; Sosabowski, Jane; Tóth, Eva; Al-Jamal, Khuloud T

doi:10.7150/ntno.23125

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Nanotheranostics 2018; 2(2):168-183. doi:10.7150/ntno.23125 This issue Cite

Research Paper

Functionalised Carbon Nanotubes Enhance Brain Delivery of Amyloid-Targeting Pittsburgh Compound B (PiB)-Derived Ligands

Pedro Miguel Costa¹, Julie Tzu-Wen Wang^1#, Jean-François Morfin^2#, Tamanna Khanum¹, Wan To¹, Jane Sosabowski³, Eva Tóth^2✉, Khuloud T Al-Jamal^1✉

1. School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, SE1 9NH, London, United Kingdom.
2. Centre de Biophysique Moléculaire, UPR 4301, CNRS, Université d'Orléans, Rue Charles Sadron CS 80054, 45071, Orléans Cedex 2, France.
3. Centre for Molecular Oncology, Bart's Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, United Kingdom.
^# Authors share equal contribution

Citation:

Costa PM, Wang JTW, Morfin JF, Khanum T, To W, Sosabowski J, Tóth E, Al-Jamal KT. Functionalised Carbon Nanotubes Enhance Brain Delivery of Amyloid-Targeting Pittsburgh Compound B (PiB)-Derived Ligands. Nanotheranostics 2018; 2(2):168-183. doi:10.7150/ntno.23125. https://www.ntno.org/v02p0168.htm

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Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterised by brain accumulation of toxic protein aggregates, including extracellular amyloid beta (Aβ) plaques, inflammation, neuronal death and progressive cognitive dysfunction. Current diagnostic modalities, based on cognitive tests, fail to detect early AD onset, thus emphasising the need to develop improved methods for pre-symptomatic disease detection.

Building on the properties of the Pittsburgh Compound B (PiB), an Aβ-binding molecule suitable to use as positron emission tomography (PET) imaging agent, and aiming at using a more clinically available modality (like magnetic ressonance imaging, MRI), PiB derivatives have been conjugated to the macrocyclic chelator 1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane (DO3A) monoamide. However, these derivatives do not readily cross the highly selective blood-brain barrier (BBB). Taking advantage of the capacity of functionalised carbon nanotubes (f-CNTs) to cross biological barriers, including the BBB, this manuscript reports on the conjugation of two PiB derivative Gd³⁺ complexes - Gd(L₂) and Gd(L₃) - to multi-walled f-CNTs (f-MWNTs) and assessment of their in vivo biodistribution and brain uptake. It is shown that Gd(L₂) and Gd(L₃) can be efficiently loaded onto different f-MWNTs, with significant improvement in brain accumulation of the conjugates compared to the free metal complexes.

Overall, this study demonstrates that f-MWNTs have potential to be used as carriers in theranostic applications involving brain delivery of BBB impermeable compounds.

Keywords: Alzheimer's disease, Aβ plaques, Pittsburgh Compound B, carbon nanotubes (CNTs), brain delivery

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APA

Costa, P.M., Wang, J.T.W., Morfin, J.F., Khanum, T., To, W., Sosabowski, J., Tóth, E., Al-Jamal, K.T. (2018). Functionalised Carbon Nanotubes Enhance Brain Delivery of Amyloid-Targeting Pittsburgh Compound B (PiB)-Derived Ligands. Nanotheranostics, 2(2), 168-183. https://doi.org/10.7150/ntno.23125.

ACS

Costa, P.M.; Wang, J.T.W.; Morfin, J.F.; Khanum, T.; To, W.; Sosabowski, J.; Tóth, E.; Al-Jamal, K.T. Functionalised Carbon Nanotubes Enhance Brain Delivery of Amyloid-Targeting Pittsburgh Compound B (PiB)-Derived Ligands. Nanotheranostics 2018, 2 (2), 168-183. DOI: 10.7150/ntno.23125.

NLM

CSE

Costa PM, Wang JTW, Morfin JF, Khanum T, To W, Sosabowski J, Tóth E, Al-Jamal KT. 2018. Functionalised Carbon Nanotubes Enhance Brain Delivery of Amyloid-Targeting Pittsburgh Compound B (PiB)-Derived Ligands. Nanotheranostics. 2(2):168-183.

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