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Evaluation of Lipid-polyethylenimine Conjugates as Biocompatible Carriers of CpG Oligodeoxynucleotides to Macrophages

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Abstract

Considering the potent immune stimulation by CpG oligodeoxynucleotides (CpGs), the development of CpG carriers is a prerequisite for efficient cancer immunotherapy. In this study, we conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)] (DSPE-PEG-NHS) with polyethylenimine (PEI) to develop a PEI-PEG-DSPE conjugate that can serve as a biocompatible and efficient CpG carrier. Five types of PEIPEG-DSPE conjugates were developed, each with different molecular weights of PEI and different degrees of DSPEPEG modification, and all exhibited significantly lower cytotoxicity. In particular, compared to CpG delivery via natural PEI, delivery with PEI (25 kDa)-PEG-DSPE and DSPE-PEG-NHS/(amine groups of PEI) at a molar ratio of 0.1 resulted in a higher uptake of CpGs into RAW264.7 cells, probably because of the presence of a hydrophobic lipid moiety. In addition, PEI-PEG-DSPE/CpG complexes triggered significant cytokine secretion (TNF-α) from RAW264.7 cells, comparable to that triggered by PEI/CpG complexes. Thus, PEI-PEG-DSPE conjugates could serve as biocompatible and efficient carriers of the immune stimulator CpG to the macrophages.

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Acknowledgements

This study was supported by a grant (NRF- 2020R1A2B 5B01001677) from the National Research Foundation funded by the Ministry of Education, Science, and Technology. The authors declare no conflicts of interest. Neither ethical approval nor informed consent was required for this study.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Bioscience and Biotechnology, Konkuk University, Seoul, 05029, Korea

    Jiwon Yang, Eun Seo Choi, Gayeon You & Hyejung Mok

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  1. Jiwon Yang
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  2. Eun Seo Choi
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Correspondence to Hyejung Mok.

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Yang, J., Choi, E.S., You, G. et al. Evaluation of Lipid-polyethylenimine Conjugates as Biocompatible Carriers of CpG Oligodeoxynucleotides to Macrophages. Biotechnol Bioproc E 26, 586–594 (2021). https://doi.org/10.1007/s12257-020-0366-1

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  • DOI: https://doi.org/10.1007/s12257-020-0366-1

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