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Title: Surface protein engineering increases the circulation time of a cell membrane-based nanotherapeutic
Authors: Krishnamurthy, Sangeetha
Muthukumaran, Padmalosini
Jayakumar, Muthu Kumara Gnanasammandhan
Lisse, Domenik
Masurkar, Nihar D.
Xu, Chenjie
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.
Project: NMRC/CSAINV17nov-0008
RG 131/15
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.
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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