Improved formulations of antisense oligodeoxynucleotides using wrapped liposomes

Yamauchi, Masahiro; Kusano, Hiroko; Saito, Etsuko; Iwata, Takeshi; Nakakura, Masashi; Kato, Yasuki; Uochi, Takaaki; Akinaga, Shiro; Aoki, Noboru

doi:10.1016/j.jconrel.2006.05.025

Cited by 14 publications

(7 citation statements)

References 19 publications

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“…The f potential is used to guide the development of liposome/nucleic acid formulations because it influences the interactions both between the particles and the cell surface and among the particles themselves. Zeta potentials compatible with the introduction of a nucleic acid into the cytoplasm are in the range 0 to 60 mV (7,33,34). The f potential of B043/LIC was 55 mV and that of B043/PEG-LIC was 48 mV, values that are compatible with both the intracellular delivery of nucleic acid and the avoidance of aggregation.…”

Section: Discussionmentioning

confidence: 96%

Tumor Regression in Mice by Delivery of Bcl-2 Small Interfering RNA with Pegylated Cationic Liposomes

et al. 2008

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The pharmacokinetics and antitumor activity of pegylated small interfering RNA (siRNA)/cationic liposome complexes were studied after systemic administration to mice. We designed pegylated-lipid carriers for achieving increased plasma concentrations of RNA and hence improved accumulation of RNA in tumors by the enhanced permeability and retention effect. We compared the pharmacokinetics of siRNA complexed with liposomes incorporating pegylated lipids with longer (C-17 or C-18), shorter (C-12 to C-16), or unsaturated (C-18:1) acyl chains. When longer acyl chains were used, the plasma concentrations of siRNA obtained were dramatically higher than when shorter or unsaturated chains were used. This may be explained by the higher gelto-liquid-crystalline phase-transition temperature (Tc) of lipids with longer acyl chains, which may form more rigid liposomes with reduced uptake by the liver. We tested a siRNA that is sequence specific for the antiapoptotic bcl-2 mRNA complexed with a pegylated liposome incorporating a C-18 lipid (PEG-LIC) by i.v. administration in a mouse model of human prostate cancer. Three-fold higher accumulation of RNA in the tumors was achieved when PEG-LIC rather than nonpegylated liposomes was used, and sequence-specific antitumor activity was observed. Our siRNA/PEG-LIC complex showed no side effects on repeated administration and the strength of its antitumor activity may be attributed to its high uptake by the tumors. Pegylation of liposomes improved the plasma retention, uptake by s.c. tumors, and antitumor activity of the encapsulated siRNA. PEG-LIC is a promising candidate for siRNA cancer therapy. [Cancer Res 2008;68(21):8843-51]

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Section: Discussionmentioning

confidence: 96%

Tumor Regression in Mice by Delivery of Bcl-2 Small Interfering RNA with Pegylated Cationic Liposomes

et al. 2008

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“…In the present study, we describe the ''wrapsome'' (WS), which is based on our previously developed nanoparticle technology (10) and was developed with the aim of making use of the EPR effect to transport native siRNA to target tumors following systemic administration. We found that, when systemically administered via the tail vein, wrapsomal siRNA (siRNA/WS) accumulated in s.c. tumors, and the siRNA was taken up by the tumor cells.…”

Section: Introductionmentioning

confidence: 99%

“…A Nanoparticle System Specifically Designed to Deliver Updated version 10.1158/0008-5472.CAN-08-3945 doi:…”

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confidence: 99%

A Nanoparticle System Specifically Designed to Deliver Short Interfering RNA Inhibits Tumor Growth In vivo

et al. 2009

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“…To overcome this problem, a drug delivery system needs to (a) protect the siRNA from degradation, (b) suppress nonspecific uptake by non-target tissues, and (c) mediate accumulation of siRNA within the target tissues and cells. WS was specifically developed to enable systemic delivery of siRNA (27). WS contains siRNA and a cationic lipofection complex in a core that is fully enveloped by a neutral lipid bilayer of hydrophilic polymers.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of SS18-SSX1 expression in synovial sarcoma by small interfering RNA enhances the focal adhesion pathway and inhibits anchorage-independent growth in vitro and tumor growth in vivo

Takenaka

Naka²,

Araki³

et al. 2010

Int J Oncol

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Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterized by a unique t(X;18) translocation resulting in expression of SS18-SSX fusion protein. In order to investigate the biological function of this fusion protein and to develop a novel therapeutic option, we examined downregulation of SS18-SSX1 expression by small interfering RNA targeting SS18-SSX1 in three human SS cell lines. Microarray analysis comparing SS18-SSX1-silenced cells with control cells in three SS cell lines showed that SS18-SSX1 mainly affected the focal adhesion pathway. In accord with the array data, silencing of SS18-SSX1 enhances adhesion to the extracellular matrix through the induction of expression of myosin light-chain kinase. Furthermore, the silencing of SS18-SSX1 inhibits anchorage-independent growth in vitro and systemic delivery of siRNA against SS18-SSX1 using a nanoparticle system inhibited tumor growth in a nude mouse xenograft model. Our results demonstrate that siRNA targeting of SS18-SSX1 has therapeutic potential for the treatment of SS.

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Improved formulations of antisense oligodeoxynucleotides using wrapped liposomes

Cited by 14 publications

References 19 publications

Tumor Regression in Mice by Delivery of Bcl-2 Small Interfering RNA with Pegylated Cationic Liposomes

Tumor Regression in Mice by Delivery of Bcl-2 Small Interfering RNA with Pegylated Cationic Liposomes

A Nanoparticle System Specifically Designed to Deliver Short Interfering RNA Inhibits Tumor Growth In vivo

Downregulation of SS18-SSX1 expression in synovial sarcoma by small interfering RNA enhances the focal adhesion pathway and inhibits anchorage-independent growth in vitro and tumor growth in vivo

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