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Lipo-PEG-PEI complex as an intracellular transporter for protein therapeutics

Authors Lin YL, Chen CH, Liu YK, Huang TH, Tsai NM, Tzou SC, Liao KW

Received 27 September 2018

Accepted for publication 17 January 2019

Published 13 February 2019 Volume 2019:14 Pages 1119—1130


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang

Yu-Ling Lin,1,* Chia-Hung Chen,2,* Yen-Ku Liu,2 Tse-Hung Huang,3–6,* Nu-Man Tsai,7,8 Shey-Cherng Tzou,2,9 Kuang-Wen Liao2,9–11

1Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, ROC; 2Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC; 3Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC; 4School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; 5Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan, ROC; 6School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan, ROC; 7School of Medical Laboratory and Biotechnology, Chung Shan Medical University; 8Department of Pathology and Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC; 9Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan, ROC; 10Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; 11Center for Intelligent Drug Systems and Smart Bio-devices, National Chiao Tung University, Hsinchu, Taiwan, ROC

*These authors contributed equally to this work

Background: Protein or peptide drugs are emerging therapeutics for treating human diseases. However, current protein drugs are typically limited to acting on extracellular/cell membrane components associated with the diseases, while intracellular delivery of recombinant proteins replaces or replenishes faulty/missing proteins and remains inadequate. In this study, we developed a convenient and efficient intracellular protein delivery vehicle.
Materials and methods: A cationic liposomal polyethylenimine and polyethylene glycol complex (LPPC) was developed to noncovalently capture proteins for protein transfer into cells via endocytosis. β-glucuronidase (βG) was used in vitro and in vivo as a model enzyme to demonstrate the enzymatic activity of the intracellular transport of a protein.
Results: The endocytosed protein/LPPC complexes escaped from lysosomes, and the bound protein dissociated from LPPC in the cytosol. The enzymatic activity of βG was well preserved after intracellular delivery in vitro and in vivo.
Conclusion: Using LPPC as an intracellular protein transporter for protein therapeutics, we illustrated that LPPC may be an effective and convenient tool for studying diseases and developing therapeutics.

Keywords: liposomal polyethylenimine and polyethylene glycol complex, LPPC, intracellular protein delivery, endocytosis, enhanced green fluorescent protein, EGFP, β-glucuronidase

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