Lipid nanoparticles fuse with cell membranes of immune cells at low temperatures leading to the loss of transfection activity.

International Journal of Pharmaceutics
Takashi NakamuraHideyoshi Harashima

Abstract

Delivering nucleic acid using a non-viral vector is a potent strategy for gene modification and controlling gene expression in immune cell therapy. Since the low-temperature storage (0-4 °C) or cryopreservation of cells are indispensable for performing immune cell therapy, we investigated the interactions between an siRNA-loaded lipid nanoparticle (LNP), a multifunctional envelope-type nanodevice (MEND) containing YSK12-C4 (YSK12-MEND), and human immune cell lines (NK-92 and Jurkat) at low-temperature and its effect on transfection activity. The YSK12-MEND readily bound to the cell membrane of NK-92 cells at low-temperature, but no internalization of the YSK12-MEND by cells was observed, even after returning the temperature to 37 °C. Gene silencing activity was completely impaired. The cause of this inhibition appears to be membrane fusion between the YSK12-MEND and cell membrane at the low-temperature. Collectively, our results suggest that the exposure of siRNA-loaded LNPs to cells at low-temperature should be avoided in defining transfection protocols in immune cell therapy.

Citations

Dec 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yusuke SatoHideyoshi Harashima
Apr 17, 2021·Advanced Materials·Arun R K KumarAndy Tay
Aug 3, 2021·The Science of the Total Environment·Aqiang DingPeili Lu
Oct 1, 2021·International Journal of Pharmaceutics·Takashi NakamuraHideyoshi Harashima

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