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

• Main Authors: Krishnamurthy, Sangeetha, Muthukumaran, Padmalosini, Jayakumar, Muthu Kumara Gnanasammandhan, Lisse, Domenik, Masurkar, Nihar D., Xu, Chenjie, Chan, Juliana M., Drum, Chester L.
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2021
• Subjects: Science::Medicine; PASylation; Nanoghosts
• Online Access: https://hdl.handle.net/10356/150808
• Institution: Nanyang Technological University

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.