Systemic delivery of small interfering RNA targeting nuclear factor κB in mice with collagen-induced arthritis using arginine-histidine-cysteine based oligopeptide-modified polymer nanomicelles

Kanazawa, Takanori; Endo, Takahiro; Arima, Naoki; Ibaraki, Hisako; Takashima, Yuuki; Seta, Yasuo

doi:10.1016/j.ijpharm.2016.10.033

Cited by 32 publications

(28 citation statements)

References 28 publications

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“…However, in our previous study, 10) the naked siRNA showed the intracellular uptake ability (5-10%) and the suppression of RelA mRNA level (30-40%) in LPS-stimulated immune-related cells, which are increased in immune-activated knee joint. In addition, it was reported that most of SC hydrogel was remained in rat skin on 3 d after injection.…”

Section: Resultsmentioning

confidence: 72%

“…8,9) Therefore, we focused that siRNA targeted against RelA, an important NF-κB subdomain and reported that the siRNA targeted against RelA (anti-RelA siRNA), an important NF-κB subdomain, was an effective therapeutic in atopic dermatitis and RA mouse model. [10][11][12] In this study, to develop a RA-treatment injectable drug/ siRNA retentionable formulation, an injectable SC hydrogel formulation containing siRNA was prepared and assessed in vitro sustained release and retention after intra-articular injection of a hydrogel formulation containing fluorescence-labeled model siRNA. Additionally, we also evaluated the therapeutic efficacy following intra-articular administration in a CIA mouse.…”

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confidence: 99%

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Intra-articular Retention and Anti-arthritic Effects in Collagen-Induced Arthritis Model Mice by Injectable Small Interfering RNA Containing Hydrogel

Kanazawa

Tamano

Sogabe

et al. 2017

Biological & Pharmaceutical Bulletin

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Small interfering RNAs (siRNAs) are expected to offer a means of treating rheumatoid arthritis (RA) because they allow the specific silencing of genes related to RA pathogenesis. In our previous study, we reported that the siRNA targeted against RelA (anti-RelA siRNA), an important nuclear factor-kappaB (NF-κB) subdomain, was an effective therapeutic in atopic dermatitis and RA model animals. In this study, to develop an intra-articular injectable gel formulation against RA, we prepared a hydrogel that contains anti-RelA siRNA, and determined the in vitro release profile (%) and in vivo intra-articular retention of fluorescence-labeled model siRNA, and the anti-arthritic effects of the anti-RelA siRelA containing hydrogel in RA model mice. We selected the silk protein, sericin (SC), as an aqueous gel base, as it is a biocompatible and useful for forming hydrogels without a cross-linker. We showed that fluorescence-labeled model siRNA was continuously released from SC hydrogel in vitro, and retained in the knee joint of rats after injection of siRNA hydrogel. In addition, the knee joint thickness, clinical severity and incidence (%) in collagen-induced arthritis (CIA) mice as RA model treated with anti-RelA siRNA containing hydrogel were more improved than untreated, anti-RelA siRNA solution and negative control siRNA containing hydrogel group. Therefore, the intra-articular injectable sericin hydrogel formulation containing of anti-RelA siRNA could be a great potential therapeutic in rheumatoid arthritis.

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Section: Resultsmentioning

confidence: 72%

mentioning

confidence: 99%

Intra-articular Retention and Anti-arthritic Effects in Collagen-Induced Arthritis Model Mice by Injectable Small Interfering RNA Containing Hydrogel

Kanazawa

Tamano

Sogabe

et al. 2017

Biological & Pharmaceutical Bulletin

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“…The MPEG-PCL-CH2R4H2C was synthesized and the conjugation reaction was confirmed as previously described [20,21]. The ratio and volume between MPEG-PCL and CH2R4H2C were at optimal values after careful consideration.…”

Section: Synthesis Of Ch2r4h2c Conjugated To Mpeg-pclmentioning

confidence: 99%

“…The inhibitory efficiency of RelA with CH2R4H2C for treatment of allergy such as atopic dermatitis or collagen-induced arthritis mice was previously reported [21,[32][33][34][35]. The carrier with CH2R4H2C is a revolutionary system that exhibits high siRNA delivery ability to inflammatory sites and has a remarkable RelA silencing effect.…”

Section: Introductionmentioning

confidence: 95%

“…Methoxy-polyethylene glycol combined polycaprolactone conjugated with a cytoplasm-responsive peptide CH2R4H2C (MPEG-PCL-CH2R4H2C) has been previously confirmed to form micelles with a particle size of 100 nm or less and has high drug accumulation in tumor-bearing mice [20,21]. Furthermore, the suppression of solid tumor growth by intravenous administration using siRNA against vascular endothelial cell growth factor (VEGF) with MPEG-PCL-CH2R4H2C was also reported [20].…”

Section: Introductionmentioning

confidence: 96%

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Anti-Metastatic Effects on Melanoma via Intravenous Administration of Anti-NF-κB siRNA Complexed with Functional Peptide-Modified Nano-Micelles

et al. 2020

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Controlling metastasis is an important strategy in cancer treatment. Nanotechnology and nucleic acids with novel modalities are promising regulators of cancer metastasis. We aimed to develop a small interfering RNA (siRNA) systemic delivery and anti-metastasis system using nanotechnology. We previously reported that polyethylene glycol-polycaprolactone (PEG-PCL) and functional peptide CH2R4H2C nano-micelle (MPEG-PCL-CH2R4H2C) has high siRNA silencing effects, indicated by increased drug accumulation in tumor-bearing mice, and has an anti-tumor effect on solid tumors upon systemic injection. In this study, we aimed to apply our micelles to inhibit metastasis and evaluated the inhibitory effect of anti-RelA siRNA (siRelA), which is a subunit of NF-κB conjugated with MPEG-PCL-CH2R4H2C, via systemic administration. We report that siRelA/MPEG-PCL-CH2R4H2C had a high cellular uptake and suppressed the migration/invasion of cells in B16F10 cells without toxicity. In addition, in a lung metastasis mouse model using intravenous administration of B16F10 cells treated with siRelA/MPEG-PCL-CH2R4H2C, the number of lung nodules in lung tissue significantly decreased compared to naked siRelA and siControl/MPEG-PCL-CH2R4H2C micelle treatments. Hence, we show that RelA expression can reduce cancer metastasis, and MPEG-PCL-CH2R4H2C is an effective siRNA carrier for anti-metastasis cancer therapies.

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Cell‐Penetrating Peptide‐Conjugated Polymer Micelle for pDNA/siRNA Delivery

Kanazawa

2022

Cell‐Penetrating Peptides

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Systemic delivery of small interfering RNA targeting nuclear factor κB in mice with collagen-induced arthritis using arginine-histidine-cysteine based oligopeptide-modified polymer nanomicelles

Cited by 32 publications

References 28 publications

Intra-articular Retention and Anti-arthritic Effects in Collagen-Induced Arthritis Model Mice by Injectable Small Interfering RNA Containing Hydrogel

Intra-articular Retention and Anti-arthritic Effects in Collagen-Induced Arthritis Model Mice by Injectable Small Interfering RNA Containing Hydrogel

Anti-Metastatic Effects on Melanoma via Intravenous Administration of Anti-NF-κB siRNA Complexed with Functional Peptide-Modified Nano-Micelles

Cell‐Penetrating Peptide‐Conjugated Polymer Micelle for pDNA/siRNA Delivery

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