Tumor-homing glycol chitosan/polyethylenimine nanoparticles for the systemic delivery of siRNA in tumor-bearing mice

Myung Sook Huh; Seung Young Lee; Sangjin Park; Seulki Lee; Hyunjin Chung; Sojin Lee; Yongseok Choi; Yu Kyoung Oh; Jae Hyung Park; Seo Young Jeong; Kuiwon Choi; Kwangmeyung Kim; Ick Chan Kwon

doi:10.1016/j.jconrel.2010.02.023

Tumor-homing glycol chitosan/polyethylenimine nanoparticles for the systemic delivery of siRNA in tumor-bearing mice

Myung Sook Huh, Seung Young Lee, Sangjin Park, Seulki Lee, Hyunjin Chung, Sojin Lee, Yongseok Choi, Yu Kyoung Oh, Jae Hyung Park, Seo Young Jeong, Kuiwon Choi, Kwangmeyung Kim, Ick Chan Kwon

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

147 Scopus citations

Abstract

Here, we designed a new nano-sized siRNA carrier system composed of biocompatible/biodegradable glycol chitosan polymer (GC) and strongly positively charged polyethylenimine (PEI) polymers. In order to make a stable and tumor-homing nano-sized carrier, each polymer was modified with hydrophobic 5β-cholanic acid, and they were simply mixed to form self-assembled GC-PEI nanoparticles (GC-PEI NPs), due to the strong hydrophobic interactions of 5β-cholanic acids in the polymers. The freshly prepared GC-PEI NPs showed a stable nanoparticle structure (350. nm) and they presented a strongly positive-charged surface (ζ potential = 23.8) that is enough to complex tightly with negatively charged RFP-siRNAs, designed for inhibiting red fluorescent protein (RFP) expression. The siRNA encapsulated nanoparticles (siRNA-GC-PEI NPs) formed more compact and stable nanoparticle structures (250. nm) at 1: 5 weight ratio of siRNA to GC-PEI nanoparticles. In vitro RFP expressing B16F10 tumor cell (RFP/B16F10) culture system, the siRNA-GC-PEI NPs presented a rapid time-dependent cellular uptake profile within 1. h. Moreover, the internalized siRNA-GC-PEI NPs lead to specific mRNA breaks down. Furthermore, our new formulation of siRNA-GC-PEI NPs presented a significant inhibition of RFP gene expression of RFP/B16F10-bearing mice, due to their higher tumor-targeting ability. These results revealed the promising potential of GC-PEI NPs as a stable and effective nano-sized siRNA delivery system for cancer treatment.

Original language	English
Pages (from-to)	134-143
Number of pages	10
Journal	Journal of Controlled Release
Volume	144
Issue number	2
DOIs	https://doi.org/10.1016/j.jconrel.2010.02.023
State	Published - Jun 2010

Bibliographical note

Funding Information:
This work was financially supported by the Real-Time Molecular Imaging Project , Global Research Laboratory , and by the National Research Foundation (Pioneer Research Center; 2009-0081523, Fusion Technology Project; 2009-0081876, and 2009k001595) of Korea funded by MEST, and by the grant to the Intramural Research Program of the KIST (Theragnosis).

Keywords

Cancer treatment
Glycol chitosan
Nanoparticle delivery system
Polyethylenimine
SiRNA
Tumor-targeting delivery

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10.1016/j.jconrel.2010.02.023

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title = "Tumor-homing glycol chitosan/polyethylenimine nanoparticles for the systemic delivery of siRNA in tumor-bearing mice",

abstract = "Here, we designed a new nano-sized siRNA carrier system composed of biocompatible/biodegradable glycol chitosan polymer (GC) and strongly positively charged polyethylenimine (PEI) polymers. In order to make a stable and tumor-homing nano-sized carrier, each polymer was modified with hydrophobic 5β-cholanic acid, and they were simply mixed to form self-assembled GC-PEI nanoparticles (GC-PEI NPs), due to the strong hydrophobic interactions of 5β-cholanic acids in the polymers. The freshly prepared GC-PEI NPs showed a stable nanoparticle structure (350. nm) and they presented a strongly positive-charged surface (ζ potential = 23.8) that is enough to complex tightly with negatively charged RFP-siRNAs, designed for inhibiting red fluorescent protein (RFP) expression. The siRNA encapsulated nanoparticles (siRNA-GC-PEI NPs) formed more compact and stable nanoparticle structures (250. nm) at 1: 5 weight ratio of siRNA to GC-PEI nanoparticles. In vitro RFP expressing B16F10 tumor cell (RFP/B16F10) culture system, the siRNA-GC-PEI NPs presented a rapid time-dependent cellular uptake profile within 1. h. Moreover, the internalized siRNA-GC-PEI NPs lead to specific mRNA breaks down. Furthermore, our new formulation of siRNA-GC-PEI NPs presented a significant inhibition of RFP gene expression of RFP/B16F10-bearing mice, due to their higher tumor-targeting ability. These results revealed the promising potential of GC-PEI NPs as a stable and effective nano-sized siRNA delivery system for cancer treatment.",

keywords = "Cancer treatment, Glycol chitosan, Nanoparticle delivery system, Polyethylenimine, SiRNA, Tumor-targeting delivery",

author = "Huh, {Myung Sook} and Lee, {Seung Young} and Sangjin Park and Seulki Lee and Hyunjin Chung and Sojin Lee and Yongseok Choi and Oh, {Yu Kyoung} and Park, {Jae Hyung} and Jeong, {Seo Young} and Kuiwon Choi and Kwangmeyung Kim and Kwon, {Ick Chan}",

note = "Funding Information: This work was financially supported by the Real-Time Molecular Imaging Project , Global Research Laboratory , and by the National Research Foundation (Pioneer Research Center; 2009-0081523, Fusion Technology Project; 2009-0081876, and 2009k001595) of Korea funded by MEST, and by the grant to the Intramural Research Program of the KIST (Theragnosis). ",

year = "2010",

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doi = "10.1016/j.jconrel.2010.02.023",

language = "English",

volume = "144",

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journal = "Journal of Controlled Release",

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T1 - Tumor-homing glycol chitosan/polyethylenimine nanoparticles for the systemic delivery of siRNA in tumor-bearing mice

AU - Huh, Myung Sook

AU - Lee, Seung Young

AU - Park, Sangjin

AU - Lee, Seulki

AU - Chung, Hyunjin

AU - Lee, Sojin

AU - Choi, Yongseok

AU - Oh, Yu Kyoung

AU - Park, Jae Hyung

AU - Jeong, Seo Young

AU - Choi, Kuiwon

AU - Kim, Kwangmeyung

AU - Kwon, Ick Chan

N1 - Funding Information: This work was financially supported by the Real-Time Molecular Imaging Project , Global Research Laboratory , and by the National Research Foundation (Pioneer Research Center; 2009-0081523, Fusion Technology Project; 2009-0081876, and 2009k001595) of Korea funded by MEST, and by the grant to the Intramural Research Program of the KIST (Theragnosis).

PY - 2010/6

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N2 - Here, we designed a new nano-sized siRNA carrier system composed of biocompatible/biodegradable glycol chitosan polymer (GC) and strongly positively charged polyethylenimine (PEI) polymers. In order to make a stable and tumor-homing nano-sized carrier, each polymer was modified with hydrophobic 5β-cholanic acid, and they were simply mixed to form self-assembled GC-PEI nanoparticles (GC-PEI NPs), due to the strong hydrophobic interactions of 5β-cholanic acids in the polymers. The freshly prepared GC-PEI NPs showed a stable nanoparticle structure (350. nm) and they presented a strongly positive-charged surface (ζ potential = 23.8) that is enough to complex tightly with negatively charged RFP-siRNAs, designed for inhibiting red fluorescent protein (RFP) expression. The siRNA encapsulated nanoparticles (siRNA-GC-PEI NPs) formed more compact and stable nanoparticle structures (250. nm) at 1: 5 weight ratio of siRNA to GC-PEI nanoparticles. In vitro RFP expressing B16F10 tumor cell (RFP/B16F10) culture system, the siRNA-GC-PEI NPs presented a rapid time-dependent cellular uptake profile within 1. h. Moreover, the internalized siRNA-GC-PEI NPs lead to specific mRNA breaks down. Furthermore, our new formulation of siRNA-GC-PEI NPs presented a significant inhibition of RFP gene expression of RFP/B16F10-bearing mice, due to their higher tumor-targeting ability. These results revealed the promising potential of GC-PEI NPs as a stable and effective nano-sized siRNA delivery system for cancer treatment.

AB - Here, we designed a new nano-sized siRNA carrier system composed of biocompatible/biodegradable glycol chitosan polymer (GC) and strongly positively charged polyethylenimine (PEI) polymers. In order to make a stable and tumor-homing nano-sized carrier, each polymer was modified with hydrophobic 5β-cholanic acid, and they were simply mixed to form self-assembled GC-PEI nanoparticles (GC-PEI NPs), due to the strong hydrophobic interactions of 5β-cholanic acids in the polymers. The freshly prepared GC-PEI NPs showed a stable nanoparticle structure (350. nm) and they presented a strongly positive-charged surface (ζ potential = 23.8) that is enough to complex tightly with negatively charged RFP-siRNAs, designed for inhibiting red fluorescent protein (RFP) expression. The siRNA encapsulated nanoparticles (siRNA-GC-PEI NPs) formed more compact and stable nanoparticle structures (250. nm) at 1: 5 weight ratio of siRNA to GC-PEI nanoparticles. In vitro RFP expressing B16F10 tumor cell (RFP/B16F10) culture system, the siRNA-GC-PEI NPs presented a rapid time-dependent cellular uptake profile within 1. h. Moreover, the internalized siRNA-GC-PEI NPs lead to specific mRNA breaks down. Furthermore, our new formulation of siRNA-GC-PEI NPs presented a significant inhibition of RFP gene expression of RFP/B16F10-bearing mice, due to their higher tumor-targeting ability. These results revealed the promising potential of GC-PEI NPs as a stable and effective nano-sized siRNA delivery system for cancer treatment.

KW - Cancer treatment

KW - Glycol chitosan

KW - Nanoparticle delivery system

KW - Polyethylenimine

KW - SiRNA

KW - Tumor-targeting delivery

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Tumor-homing glycol chitosan/polyethylenimine nanoparticles for the systemic delivery of siRNA in tumor-bearing mice

Abstract

Bibliographical note

Keywords

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