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|Title:||Surface protein engineering increases the circulation time of a cell membrane-based nanotherapeutic||Authors:||Krishnamurthy, Sangeetha
Jayakumar, Muthu Kumara Gnanasammandhan
Masurkar, Nihar D.
Chan, Juliana M.
Drum, Chester L.
|Keywords:||Science::Medicine||Issue Date:||2019||Source:||Krishnamurthy, S., Muthukumaran, P., Jayakumar, M. K. G., Lisse, D., Masurkar, N. D., Xu, C., Chan, J. M. & Drum, C. L. (2019). Surface protein engineering increases the circulation time of a cell membrane-based nanotherapeutic. Nanomedicine: Nanotechnology, Biology, and Medicine, 18, 169-178. https://dx.doi.org/10.1016/j.nano.2019.02.024||Project:||NMRC/CSAINV17nov-0008
|Journal:||Nanomedicine: Nanotechnology, Biology, and Medicine||Abstract:||Mammalian cell membranes are often incompatible with chemical modifications typically used to increase circulation half-life. Using cellular nanoghosts as a model, we show that proline-alanine-serine (PAS) peptide sequences expressed on the membrane surface can extend the circulation time of a cell membrane derived nanotherapeutic. Membrane expression of a PAS 40 repeat sequence decreased protein binding and resulted in a 90% decrease in macrophage uptake when compared with non-PASylated controls (P ≤ 0.05). PASylation also extended circulation half-life (t1/2 = 37 h) compared with non-PASylated controls (t1/2 = 10.5 h) (P ≤ 0.005), resulting in ~7-fold higher in vivo serum concentrations at 24 h and 48 h (P ≤ 0.005). Genetically engineered membrane expression of PAS repeats may offer an alternative to PEGylation and provide extended circulation times for cellular membrane-derived nanotherapeutics.||URI:||https://hdl.handle.net/10356/150808||ISSN:||1549-9634||DOI:||10.1016/j.nano.2019.02.024||Rights:||© 2019 Elsevier Inc. All rights reserved.||Fulltext Permission:||none||Fulltext Availability:||No Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
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