Preparation of PEGylated cationic nanoliposome-siRNA complexes for cancer therapy

F. Haghiralsadat; G. Amoabediny; S. Naderinezhad; T. Forouzanfar; M.N. Helder; B. Zandieh-Doulabi

doi:10.1080/21691401.2018.1434533

Preparation of PEGylated cationic nanoliposome-siRNA complexes for cancer therapy

F. Haghiralsadat, G. Amoabediny, S. Naderinezhad, T. Forouzanfar, M.N. Helder, B. Zandieh-Doulabi

Maxillofacial Surgery (VUmc)

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Cationic liposomes have been investigated as non-viral vectors for gene delivery for more than a decade to overcome challenges associated with viral gene delivery. However, due to instability of liposomes, siRNA delivery is still a serious problem. In this study, we developed stealth PEGylated liposome formulations and focused on the effects of PEGylated liposomes on parameters related to size, zeta potential, polydispersity index, siRNA-loading efficiency and long-term stability of the siRNA-liposome complex. We were able to generate siRNA lipoplexes that could be very efficiently loaded, did not aggregate, could be stored at 4 °C for at least 6 months with only marginal release (1–5%) of siRNA and enhanced intracellular delivery of siRNA. Moreover, we could demonstrate that PEGylation positively contributed to all these parameters compared to liposomes, which were not PEGylated. The prepared lipoplex was successfully silenced J1P1 expression in MG-63 osteosarcoma cell line. In conclusion, our novel PEGylated liposomes have high potential for systemic delivery of siRNA and can improve in vivo stability of free siRNA and also siRNA lipoplexes.

Original language	English
Pages (from-to)	684-692
Journal	Artificial Cells, Nanomedicine and Biotechnology
Volume	46
Issue number	S1
DOIs	https://doi.org/10.1080/21691401.2018.1434533
Publication status	Published - 2018

Funding

aDepartment of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran; bDepartment of Biotechnology and Pharmaceutical Engineering, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran; cDepartment of Oral and Maxillofacial Surgery, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, Netherlands We thank Fateme Hakimian and Fateme Montazeri researcher from Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran, and Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran, respectively, for scientific assistance during the project.

Funders	Funder number
Vrije Universiteit Amsterdam
University of Tehran
Shahid Sadoughi University of Medical Sciences
of Biotechnology and Pharmaceutical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/21691401.2018.1434533

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title = "Preparation of PEGylated cationic nanoliposome-siRNA complexes for cancer therapy",

abstract = "Cationic liposomes have been investigated as non-viral vectors for gene delivery for more than a decade to overcome challenges associated with viral gene delivery. However, due to instability of liposomes, siRNA delivery is still a serious problem. In this study, we developed stealth PEGylated liposome formulations and focused on the effects of PEGylated liposomes on parameters related to size, zeta potential, polydispersity index, siRNA-loading efficiency and long-term stability of the siRNA-liposome complex. We were able to generate siRNA lipoplexes that could be very efficiently loaded, did not aggregate, could be stored at 4 °C for at least 6 months with only marginal release (1–5%) of siRNA and enhanced intracellular delivery of siRNA. Moreover, we could demonstrate that PEGylation positively contributed to all these parameters compared to liposomes, which were not PEGylated. The prepared lipoplex was successfully silenced J1P1 expression in MG-63 osteosarcoma cell line. In conclusion, our novel PEGylated liposomes have high potential for systemic delivery of siRNA and can improve in vivo stability of free siRNA and also siRNA lipoplexes.",

author = "F. Haghiralsadat and G. Amoabediny and S. Naderinezhad and T. Forouzanfar and M.N. Helder and B. Zandieh-Doulabi",

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language = "English",

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AU - Haghiralsadat, F.

AU - Amoabediny, G.

AU - Naderinezhad, S.

AU - Forouzanfar, T.

AU - Helder, M.N.

AU - Zandieh-Doulabi, B.

PY - 2018

Y1 - 2018

N2 - Cationic liposomes have been investigated as non-viral vectors for gene delivery for more than a decade to overcome challenges associated with viral gene delivery. However, due to instability of liposomes, siRNA delivery is still a serious problem. In this study, we developed stealth PEGylated liposome formulations and focused on the effects of PEGylated liposomes on parameters related to size, zeta potential, polydispersity index, siRNA-loading efficiency and long-term stability of the siRNA-liposome complex. We were able to generate siRNA lipoplexes that could be very efficiently loaded, did not aggregate, could be stored at 4 °C for at least 6 months with only marginal release (1–5%) of siRNA and enhanced intracellular delivery of siRNA. Moreover, we could demonstrate that PEGylation positively contributed to all these parameters compared to liposomes, which were not PEGylated. The prepared lipoplex was successfully silenced J1P1 expression in MG-63 osteosarcoma cell line. In conclusion, our novel PEGylated liposomes have high potential for systemic delivery of siRNA and can improve in vivo stability of free siRNA and also siRNA lipoplexes.

AB - Cationic liposomes have been investigated as non-viral vectors for gene delivery for more than a decade to overcome challenges associated with viral gene delivery. However, due to instability of liposomes, siRNA delivery is still a serious problem. In this study, we developed stealth PEGylated liposome formulations and focused on the effects of PEGylated liposomes on parameters related to size, zeta potential, polydispersity index, siRNA-loading efficiency and long-term stability of the siRNA-liposome complex. We were able to generate siRNA lipoplexes that could be very efficiently loaded, did not aggregate, could be stored at 4 °C for at least 6 months with only marginal release (1–5%) of siRNA and enhanced intracellular delivery of siRNA. Moreover, we could demonstrate that PEGylation positively contributed to all these parameters compared to liposomes, which were not PEGylated. The prepared lipoplex was successfully silenced J1P1 expression in MG-63 osteosarcoma cell line. In conclusion, our novel PEGylated liposomes have high potential for systemic delivery of siRNA and can improve in vivo stability of free siRNA and also siRNA lipoplexes.

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DO - 10.1080/21691401.2018.1434533

M3 - Article

SN - 2169-1401

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JO - Artificial Cells, Nanomedicine and Biotechnology

JF - Artificial Cells, Nanomedicine and Biotechnology

IS - S1

ER -

Preparation of PEGylated cationic nanoliposome-siRNA complexes for cancer therapy

Abstract

Funding

UN SDGs

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