A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells

Warashina, Shota; Nakamura, Takashi; Sato, Yusuke; Fujiwara, Yuki; Hyodo, Mamoru; Hatakeyama, Hiroto; Harashima, Hideyoshi

doi:10.1016/j.jconrel.2016.01.042

Cited by 102 publications

(103 citation statements)

References 34 publications

(55 reference statements)

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“…The YSK12-MEND used in this study was composed of YSK12-C4, cholesterol, 1,2-dimyristoyl-sn-glycerol methoxyethyleneglycol 2000 ether (PEG-DMG) (85/15/1 mol ratio) and siRNA15. Although YSK12-C4 is an ionizable-cationic lipid, the pKa of the YSK12-MEND is 8.0.…”

Section: Resultsmentioning

confidence: 99%

“…In a previous study, we developed a multifunctional envelope-type nanodevice (MEND) for use as a non-viral delivery system14 and reported that a MEND containing YSK12-C4 lipid (YSK12-MEND) can be used to deliver siRNA to mouse DC15. YSK12-C4 is an ionizable-cationic lipid containing unsaturated carbon chains, which facilitate efficient endosomal escape.…”

mentioning

confidence: 99%

“…YSK12-C4 is an ionizable-cationic lipid containing unsaturated carbon chains, which facilitate efficient endosomal escape. The use of the YSK12-MEND resulted in a gene silencing efficiency in excess of 90%, with a median effective dose (ED 50 ) of 1.5 nM in mouse DC15. The gene silencing ability of the YSK12-MEND was much higher than that of RNAiMAX (ED 50 was 25 nM).…”

mentioning

confidence: 99%

“…The gene silencing ability of the YSK12-MEND was much higher than that of RNAiMAX (ED 50 was 25 nM). In addition, the silencing of suppressor of cytokine signaling 1, an immune suppressive molecule, by the YSK12-MEND drastically enhanced cytokine production in mouse DC, resulting in a significant suppression of tumor growth when it was applied to DC-based therapy against a mouse lymphoma15. Therefore, we hypothesized that the YSK12-MEND would be able to induce efficient gene silencing in human immune cells.…”

mentioning

confidence: 99%

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Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines

Nakamura

Kuroi

Fujiwara

et al. 2016

Sci Rep

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Gene silencing by small interfering RNA (siRNA) is useful for analyzing the functions of human immune cells. However, the transfection of siRNA to human immune cells is difficult. Here, we used a multifunctional envelope-type nanodevice (MEND) containing YSK12-C4 (YSK12-MEND) to efficiently introduce siRNA to human immune cell lines, Jurkat, THP-1, KG-1 and NK92. The YSK12-MEND was transfected to human immune cell lines at a siRNA dose range of 1–30 nM, resulting that maximum gene silencing efficiencies at the mRNA level in Jurkat, THP-1, KG-1 and NK92 were 96%, 96%, 91% and 75%, respectively. The corresponding values for Lipofectamine RNAiMAX (RNAiMAX) were 37%, 56%, 43% and 19%, respectively. The process associated with cellular uptake played a role in effective gene silencing effect of the YSK12-MEND. The small size and high non-aggregability of the YSK12-MEND were advantageous for the cellular internalization of siRNA to immune cell lines. In the case of RNAiMAX, a drastic increase in particles size was observed in the medium used, which inhibited cellular uptake. The YSK12-MEND reported in herein appears to be appropriate for delivering siRNA to human immune cells, and the small particle size and non-aggregability are essential properties.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines

Nakamura

Kuroi

Fujiwara

et al. 2016

Sci Rep

Self Cite

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“…The phagocytosis capability of macrophages from UCNPs treated mice was increased, demonstrating that NPs can stimulate innate immune response in vivo [87]. Recently, small interfering RNA (siRNA) modified NPs showed drastic gene silencing efficiency against the suppressor of cytokine signaling 1(SOCS1) gene in mouse DCs, leading to enhanced TNF-α and IL-6 production, and inhibited tumor growth in lymphoma bearing mice [88]. …”

Section: Therapeutic Immune Modulation By Engineered Nanoparticlesmentioning

confidence: 99%

Effects of engineered nanoparticles on the innate immune system

Liu

Hardie

Zhang

et al. 2017

Seminars in Immunology

220

146

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Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system. NPs size, shape, hydrophobicity and surface modification are the main factors that influence the interactions between NPs and the innate immune system. In this review, we will focus on recent reports about the relationship between the physicochemical properties of NPs and their innate immune response, and their applications in immunotherapy.

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Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy

Lü

Laney

Hall

et al. 2020

Adv Healthcare Materials

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RNA interference (RNAi) is a promising technology to regulate oncogenes for treating cancer. The primary limitation of siRNA for clinical application is the safe and efficacious delivery of therapeutic siRNA into target cells. Lipid‐based delivery systems are developed to protect siRNA during the delivery process and to facilitate intracellular uptake. There is a significant progress in lipid nanoparticle systems that utilize cationic and protonatable amino lipid systems to deliver siRNA to tumors. Among these lipids, environment‐responsive lipids are a class of novel lipid delivery systems that are capable of responding to the environment changes during the delivery process and demonstrate great promise for clinical translation for siRNA therapeutics. Protonatable or ionizable amino lipids and switchable lipids as well as pH‐sensitive multifunctional amino lipids are the presentative environment‐responsive lipids for siRNA delivery. These lipids are able to respond to environmental changes during the delivery process to facilitate efficient cytosolic siRNA delivery. Environment‐responsive lipid/siRNA nanoparticles (ERLNP) are developed with the lipids and are tested for efficient delivery of therapeutic siRNA into the cytoplasm of cancer cells to silence target genes for cancer treatment in preclinical development. This review summarizes the recent developments in environment‐response lipids and nanoparticles for siRNA delivery in cancer therapy.

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A lipid nanoparticle for the efficient delivery of siRNA to dendritic cells

Cited by 102 publications

References 34 publications

Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines

Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines

Effects of engineered nanoparticles on the innate immune system

Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy

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