Surface protein engineering increases the circulation time of a cell membrane-based nanotherapeutic

Publication date: June 2019Source: Nanomedicine: Nanotechnology, Biology and Medicine, Volume 18Author(s): Sangeetha Krishnamurthy, Padmalosini Muthukumaran, Muthu Kumara Gnanasammandhan Jayakumar, Domenik Lisse, Nihar D. Masurkar, Chenjie Xu, Juliana M. Chan, Chester L. DrumAbstractMammalian 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.Graphical AbstractExpressing the genetically engineered unstructured PAS protein on the surface of cellular nanoghosts greatly extends circulation time in vivo.
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research