Efficient Delivery of Globotriaosylceramide Synthase siRNA using Polyhistidine-Incorporated Lipid Nanoparticles

In Gyu Kim, Won Ho Jung, Gayeon You, Hyukjin Lee, Yoo Jin Shin, Sun Woo Lim, Byung Ha Chung, Hyejung Mok

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


In this study, a novel polyhistidine-incorporated lipid nanoparticle (pHis/LNP) is developed for the delivery of therapeutic globotriaosylceramide (Gb3) synthase siRNAs using a microfluidic device with pHis as a biocompatible method of endosome escape. To inhibit the expression of Gb3 synthase, six siRNAs against Gb3 synthase are designed and an optimal siRNA sequence is selected. Selected Gb3 synthase siRNA is incorporated into pHis/LNP to prepare a spherical siRNA pHis/LNP with a size of 62.5 ± 1.9 nm and surface charge of −13.3 ± 4.2 mV. The pHis/LNP successfully protects siRNAs from degradation in 50% serum condition for 72 h. Prepared pHis/LNP exhibits superior stability for 20 days and excellent biocompatibility for A549 cells. After treatment with fluorescence-labeled LNPs, dotted fluorescent signals are co-localized with Lysotracker in cells with LNPs, whereas strong and diffused fluorescence intensity is observed in cells with pHis/LNPs probably due to successful endosomal escape. The extent of Gb3 synthase gene silencing by siRNA pHis/LNP is greatly improved (6.0-fold) compared to that by siRNA/LNP. Taken together, considering that the fabricated siRNA pHis/LNP exhibits excellent biocompatibility and superior gene silencing activity over conventional LNP, these particles can be utilized for the delivery of a wide range of therapeutic siRNAs.

Original languageEnglish
Article number2200423
JournalMacromolecular Bioscience
Issue number4
StatePublished - Apr 2023

Bibliographical note

Funding Information:
I.G.K. and W.H.J. contributed equally to this work. This study was supported by the Ministry of Health and Welfare, Republic of Korea (grant no. HI22C0537) and the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology of Korea (grant no. NRF‐ 2020R1A2B5B01001677).

Publisher Copyright:
© 2023 Wiley-VCH GmbH.


  • endosome escape
  • globotriaosylceramide synthase
  • lipid nanoparticles
  • polyhistidine
  • siRNA


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