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Nanomedicine. 2019 Jun;18:169-178. doi: 10.1016/j.nano.2019.02.024. Epub 2019 Mar 8.

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

Author information

1
Cardiovascular Research Institute, National University Health System, Singapore; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
2
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
3
Cardiovascular Research Institute, National University Health System, Singapore.
4
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, Singapore.
5
Cardiovascular Research Institute, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: mdccld@nus.edu.sg.

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.

KEYWORDS:

Cell ghosts; Drug delivery; Lipid-polymer hybrid nanoparticles; Nanoghosts; Nanomedicine; PASylation; Synthetic biology

PMID:
30853651
DOI:
10.1016/j.nano.2019.02.024

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