Delivery of siRNA Using Lipid Nanoparticles Modified with Cell Penetrating Peptide

Yuhuan Li; Robert J. Lee; Kongtong Yu; Ye Bi; Yuhang Qi; Yating Sun; Yujing Li; Jing Xie; Lesheng Teng

doi:10.1021/acsami.6b09991

Delivery of siRNA Using Lipid Nanoparticles Modified with Cell Penetrating Peptide

Yuhuan Li, Robert J. Lee, Kongtong Yu, Ye Bi, Yuhang Qi, Yating Sun, Yujing Li, Jing Xie^*, Lesheng Teng

^*Corresponding author for this work

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

53 Citations (Scopus)

Abstract

Clinical development of siRNA has been hindered by the lack of an effective delivery system. Here, we report the construction of a novel siRNA delivery system, sTOLP, which is based on cell penetrating peptide oleoyl-octaarginine (OA-R8) modified multifunctional lipid nanoparticles. sTOLP nanoparticles are composed of a protamine complexed siRNA core, OA-R8, cationic and PEGylated lipids, and transferrin as a targeting ligand. sTOLP formulation was optimized and characterized in vitro and showed excellent gene silencing activity. In vivo, siRNA encapsulated in sTOLP exhibited potent tumor inhibition (61.7%) and was preferentially taken up by hepatocytes and tumor cells in HepG2-bearing nude mice without inducing immunogenicity or hepatic or renal toxicity. Furthermore, sTOLP-loaded siRNA had stability in circulation greater than that of free siRNA. These data demonstrated potential utility of sTOLP-mediated siRNA delivery in cancer therapy.

Original language	English
Pages (from-to)	26613-26621
Number of pages	9
Journal	ACS applied materials & interfaces
Volume	8
Issue number	40
DOIs	https://doi.org/10.1021/acsami.6b09991
Publication status	Published - 12 Oct 2016
Externally published	Yes

Keywords

cancer
cell penetrating peptide
drug delivery
lipid nanoparticles
multifunctional
siRNA

UN SDGs

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

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10.1021/acsami.6b09991

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title = "Delivery of siRNA Using Lipid Nanoparticles Modified with Cell Penetrating Peptide",

abstract = "Clinical development of siRNA has been hindered by the lack of an effective delivery system. Here, we report the construction of a novel siRNA delivery system, sTOLP, which is based on cell penetrating peptide oleoyl-octaarginine (OA-R8) modified multifunctional lipid nanoparticles. sTOLP nanoparticles are composed of a protamine complexed siRNA core, OA-R8, cationic and PEGylated lipids, and transferrin as a targeting ligand. sTOLP formulation was optimized and characterized in vitro and showed excellent gene silencing activity. In vivo, siRNA encapsulated in sTOLP exhibited potent tumor inhibition (61.7%) and was preferentially taken up by hepatocytes and tumor cells in HepG2-bearing nude mice without inducing immunogenicity or hepatic or renal toxicity. Furthermore, sTOLP-loaded siRNA had stability in circulation greater than that of free siRNA. These data demonstrated potential utility of sTOLP-mediated siRNA delivery in cancer therapy.",

keywords = "cancer, cell penetrating peptide, drug delivery, lipid nanoparticles, multifunctional, siRNA",

author = "Yuhuan Li and Lee, {Robert J.} and Kongtong Yu and Ye Bi and Yuhang Qi and Yating Sun and Yujing Li and Jing Xie and Lesheng Teng",

note = "Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

year = "2016",

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doi = "10.1021/acsami.6b09991",

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AU - Li, Yuhuan

AU - Lee, Robert J.

AU - Yu, Kongtong

AU - Bi, Ye

AU - Qi, Yuhang

AU - Sun, Yating

AU - Li, Yujing

AU - Xie, Jing

AU - Teng, Lesheng

PY - 2016/10/12

Y1 - 2016/10/12

N2 - Clinical development of siRNA has been hindered by the lack of an effective delivery system. Here, we report the construction of a novel siRNA delivery system, sTOLP, which is based on cell penetrating peptide oleoyl-octaarginine (OA-R8) modified multifunctional lipid nanoparticles. sTOLP nanoparticles are composed of a protamine complexed siRNA core, OA-R8, cationic and PEGylated lipids, and transferrin as a targeting ligand. sTOLP formulation was optimized and characterized in vitro and showed excellent gene silencing activity. In vivo, siRNA encapsulated in sTOLP exhibited potent tumor inhibition (61.7%) and was preferentially taken up by hepatocytes and tumor cells in HepG2-bearing nude mice without inducing immunogenicity or hepatic or renal toxicity. Furthermore, sTOLP-loaded siRNA had stability in circulation greater than that of free siRNA. These data demonstrated potential utility of sTOLP-mediated siRNA delivery in cancer therapy.

AB - Clinical development of siRNA has been hindered by the lack of an effective delivery system. Here, we report the construction of a novel siRNA delivery system, sTOLP, which is based on cell penetrating peptide oleoyl-octaarginine (OA-R8) modified multifunctional lipid nanoparticles. sTOLP nanoparticles are composed of a protamine complexed siRNA core, OA-R8, cationic and PEGylated lipids, and transferrin as a targeting ligand. sTOLP formulation was optimized and characterized in vitro and showed excellent gene silencing activity. In vivo, siRNA encapsulated in sTOLP exhibited potent tumor inhibition (61.7%) and was preferentially taken up by hepatocytes and tumor cells in HepG2-bearing nude mice without inducing immunogenicity or hepatic or renal toxicity. Furthermore, sTOLP-loaded siRNA had stability in circulation greater than that of free siRNA. These data demonstrated potential utility of sTOLP-mediated siRNA delivery in cancer therapy.

KW - cancer

KW - cell penetrating peptide

KW - drug delivery

KW - lipid nanoparticles

KW - multifunctional

KW - siRNA

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SN - 1944-8244

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JO - ACS applied materials & interfaces

JF - ACS applied materials & interfaces

IS - 40

ER -

Delivery of siRNA Using Lipid Nanoparticles Modified with Cell Penetrating Peptide

Abstract

Keywords

UN SDGs

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