Imidazolized magnetic nanovectors with endosome disrupting moieties for the intracellular delivery and imaging of siRNA

Eunjung Kim; Hwunjae Lee; Yonghee An; Eunji Jang; Eun Kyung Lim; Byunghoon Kang; Jin Suck Suh; Yong Min Huh; Seungjoo Haam

doi:10.1039/c4tb01274g

Imidazolized magnetic nanovectors with endosome disrupting moieties for the intracellular delivery and imaging of siRNA

Eunjung Kim, Hwunjae Lee, Yonghee An, Eunji Jang, Eun Kyung Lim, Byunghoon Kang, Jin Suck Suh, Yong Min Huh, Seungjoo Haam

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

10 Citations (Scopus)

Abstract

The development of a synchronized delivery and imaging system for small interfering RNA (siRNA) is required for the clinical application of RNA interference (RNAi) in cancer treatment. Herein, we report a pH-responsive, magnetic nanoparticle-based siRNA delivery system that can facilitate the safe and efficient delivery and visualization of therapeutic siRNA by high-resolution magnetic resonance (MR) imaging. Cationic poly-l-lysine-graft-imidazole (PLI) with a reactive silane moiety was stably immobilized onto the surface of the assembled manganese ferrite nanoparticles (MFs) through an emulsion process, ensuring high water solubility, enhanced MR contrast effect, and endosome-disrupting functionality. The synthesized nanovectors were then complexed with siRNA targeting the CD44 gene via electrostatic interactions to verify the specific gene-silencing effect. The imidazolized magnetic nanovector (ImMNV) architectures developed here facilitated improved cellular internalization and exhibited a high level in vitro downregulation compared to non-imidazolized MNVs in metastatic breast cancer cells.

Original language	English
Pages (from-to)	8566-8575
Number of pages	10
Journal	Journal of Materials Chemistry B
Volume	2
Issue number	48
DOIs	https://doi.org/10.1039/c4tb01274g
Publication status	Published - 2014 Dec 28

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© The Royal Society of Chemistry.

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Chemistry(all)
Biomedical Engineering
Materials Science(all)

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title = "Imidazolized magnetic nanovectors with endosome disrupting moieties for the intracellular delivery and imaging of siRNA",

abstract = "The development of a synchronized delivery and imaging system for small interfering RNA (siRNA) is required for the clinical application of RNA interference (RNAi) in cancer treatment. Herein, we report a pH-responsive, magnetic nanoparticle-based siRNA delivery system that can facilitate the safe and efficient delivery and visualization of therapeutic siRNA by high-resolution magnetic resonance (MR) imaging. Cationic poly-l-lysine-graft-imidazole (PLI) with a reactive silane moiety was stably immobilized onto the surface of the assembled manganese ferrite nanoparticles (MFs) through an emulsion process, ensuring high water solubility, enhanced MR contrast effect, and endosome-disrupting functionality. The synthesized nanovectors were then complexed with siRNA targeting the CD44 gene via electrostatic interactions to verify the specific gene-silencing effect. The imidazolized magnetic nanovector (ImMNV) architectures developed here facilitated improved cellular internalization and exhibited a high level in vitro downregulation compared to non-imidazolized MNVs in metastatic breast cancer cells.",

author = "Eunjung Kim and Hwunjae Lee and Yonghee An and Eunji Jang and Lim, {Eun Kyung} and Byunghoon Kang and Suh, {Jin Suck} and Huh, {Yong Min} and Seungjoo Haam",

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year = "2014",

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doi = "10.1039/c4tb01274g",

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AU - Kim, Eunjung

AU - Lee, Hwunjae

AU - An, Yonghee

AU - Jang, Eunji

AU - Lim, Eun Kyung

AU - Kang, Byunghoon

AU - Suh, Jin Suck

AU - Huh, Yong Min

AU - Haam, Seungjoo

PY - 2014/12/28

Y1 - 2014/12/28

N2 - The development of a synchronized delivery and imaging system for small interfering RNA (siRNA) is required for the clinical application of RNA interference (RNAi) in cancer treatment. Herein, we report a pH-responsive, magnetic nanoparticle-based siRNA delivery system that can facilitate the safe and efficient delivery and visualization of therapeutic siRNA by high-resolution magnetic resonance (MR) imaging. Cationic poly-l-lysine-graft-imidazole (PLI) with a reactive silane moiety was stably immobilized onto the surface of the assembled manganese ferrite nanoparticles (MFs) through an emulsion process, ensuring high water solubility, enhanced MR contrast effect, and endosome-disrupting functionality. The synthesized nanovectors were then complexed with siRNA targeting the CD44 gene via electrostatic interactions to verify the specific gene-silencing effect. The imidazolized magnetic nanovector (ImMNV) architectures developed here facilitated improved cellular internalization and exhibited a high level in vitro downregulation compared to non-imidazolized MNVs in metastatic breast cancer cells.

AB - The development of a synchronized delivery and imaging system for small interfering RNA (siRNA) is required for the clinical application of RNA interference (RNAi) in cancer treatment. Herein, we report a pH-responsive, magnetic nanoparticle-based siRNA delivery system that can facilitate the safe and efficient delivery and visualization of therapeutic siRNA by high-resolution magnetic resonance (MR) imaging. Cationic poly-l-lysine-graft-imidazole (PLI) with a reactive silane moiety was stably immobilized onto the surface of the assembled manganese ferrite nanoparticles (MFs) through an emulsion process, ensuring high water solubility, enhanced MR contrast effect, and endosome-disrupting functionality. The synthesized nanovectors were then complexed with siRNA targeting the CD44 gene via electrostatic interactions to verify the specific gene-silencing effect. The imidazolized magnetic nanovector (ImMNV) architectures developed here facilitated improved cellular internalization and exhibited a high level in vitro downregulation compared to non-imidazolized MNVs in metastatic breast cancer cells.

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Imidazolized magnetic nanovectors with endosome disrupting moieties for the intracellular delivery and imaging of siRNA

Abstract

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