The delivery of mRNA to colon inflammatory lesions by lipid-nano-particles containing environmentally-sensitive lipid-like materials with oleic acid scaffolds

Tanaka, Hiroki; Watanabe, Ayaka; Konishi, Manami; Nakai, Yoshihisa; Yoshioka, Hiroki; Ohkawara, Tatsuya; Takeda, Hiroshi; Harashima, Hideyoshi; Akita, Hidetaka

doi:10.1016/j.heliyon.2018.e00959

Cited by 22 publications

(15 citation statements)

References 18 publications

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“…A conventional ssPalm with oleic acid scaffolds (ssPalmO) was selected as a seed material for molecular tuning, because of its less inflammatory nature. [43] As a selfdegradable material, a phenyl ester unit was inserted as a linker between the amine and the oleic acid to develop the ssPalmO-Phe. A benzyl ester was inserted as a linker (ssPalmO-Ben) as a nondegradable counterpart.…”

Section: Molecular Design Of the Sspalmo-phementioning

confidence: 99%

Self‐Degradable Lipid‐Like Materials Based on “Hydrolysis accelerated by the intra‐Particle Enrichment of Reactant (HyPER)” for Messenger RNA Delivery

Tanaka

Takahashi

Konishi

et al. 2020

Adv Funct Materials

Self Cite

106

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RNA-based therapeutics is a promising approach for curing intractable diseases by manipulating various cellular functions. For eliciting RNA (i.e., mRNA and siRNA) functions successfully, the RNA in the extracellular space must be protected and it must be delivered to the cytoplasm. In this study, the development of a self-degradable lipid-like material that functions to accelerate the collapse of lipid nanoparticles (LNPs) and the release of RNA into cytoplasm is reported. The self-degradability is based on a unique reaction "Hydrolysis accelerated by intra-Particle Enrichment of Reactant (HyPER)." In this reaction, a disulfide bond and a phenyl ester are essential structural components: concentrated hydrophobic thiols that are produced by the cleavage of the disulfide bonds in the LNPs drive an intraparticle nucleophilic attack to the phenyl ester linker, which results in further degradation. An oleic acid-scaffold lipid-like material that mounts all of these units (ssPalmO-Phe) shows superior transfection efficiency to nondegradable or conventional materials. The insertion of the aromatic ring is unexpectedly revealed to contribute to the enhancement of endosomal escape. Since the intracellular trafficking is a sequential process that includes cellular uptake, endosomal escape, the release of mRNA, and translation, the improvement in each process synergistically enhances the gene expression.

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Section: Molecular Design Of the Sspalmo-phementioning

confidence: 99%

Self‐Degradable Lipid‐Like Materials Based on “Hydrolysis accelerated by the intra‐Particle Enrichment of Reactant (HyPER)” for Messenger RNA Delivery

Tanaka

Takahashi

Konishi

et al. 2020

Adv Funct Materials

Self Cite

106

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“…The reducing conditions in the cytoplasm lead to a cleavage of the disulfide bonds in the coatsomes resulting in siRNA release. Thereby the siRNA is protected from early degradation and is directed to its target mRNA (28, 29).…”

Section: Resultsmentioning

confidence: 99%

Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand Adjuvant

et al. 2019

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Infectious diseases remain one of the leading causes of death worldwide. Vaccination is a powerful instrument to avert a variety of those by inducing a pathogen-specific immune response and ensure a long-lasting protection against the respective infection. Nevertheless, due to increasing numbers of immunocompromised patients and emergence of more aggressive pathogens existing vaccination techniques are limited. In our study we investigated a new strategy to strengthen vaccine adjuvant in order to increase immunity against infectious diseases. The strategy is based on an amplification of Toll-like receptor 4 (TLR4) -induced activation of antigen-presenting cells (APCs) by turning off a powerful endogenous inhibitor of APC-activation. TLR4 signaling induces the release of cytokines that bind autocrine and paracrine to receptors, activating the Janus kinase (JAK) 2/signal transducers and activators of transcription (STAT) 3 cascade. Subsequently, STAT3 induces expression of suppressor of cytokine signaling (SOCS) 1 that terminates the inflammatory response. In the approach, TLR4-adjuvant monophosphoryl lipid A (MPLA)-stimulated monocyte-activation is reinforced and sustained by silencing SOCS1 via lipid nanoparticle-enclosed siRNA (L-siRNA). L-siRNA is transported into primary cells without any toxic side effects and protected from early degradation. Through lipid core-embedded functional groups the lipid particle escapes from endosomes and releases the siRNA when translocated into the cytoplasm. SOCS1 is potently silenced, and SOCS1-mediated termination of NFκB signaling is abrogated. Consequently, the MPLA-stimulated activation of APCs, monitored by release of pro-inflammatory cytokines such as IL-6, TNFα, and IL-1β, upregulation of MHC class II molecules and costimulatory CD80/CD86 is strongly enhanced and prolonged. SOCS1-silenced APCs, pulsed with liposomal tetanus light chain toxin (TeTxLC) antigen, activate autologous T cells much more intensively than SOCS1-expressing cells. Importantly, expansion of cocultured CD4 + as well as CD8 + T cells is remarkably enhanced. Furthermore, our results point toward a broad T helper cell response as TH1 typical as well as TH2 characteristic cytokines are elevated. Taken together, this study in the human system comprises a translational potential to develop more effective vaccines against infectious diseases by inhibition of the endogenous negative-feedback loop in APCs.

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“…The main constituents of SBT oil include Fatty acids (such as Myristic acid, Palmitic acid, Palmitoleic acid, Oleic acid, etc), Sitosterol and β-carotene. Fatty acids are crucial components of cell membranes and play important role in biological function of cells [34]. Some of the Fatty acids are required for innate immune activation and pathogen defense [35].…”

Section: Discussionmentioning

confidence: 99%

Ameliorative effects of sea buckthorn oil on DNCB induced atopic dermatitis model mice via regulation the balance of Th1/Th2

Wang

Liu³

et al. 2020

BMC Complement Med Ther

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Background: Atopic dermatitis (AD) is a worldwide chronic skin disease which burden public health. Sea buckthorn (SBT) (Hippophae rhamnoides L., Elaeagnaceae) oil, as a traditional herbal medicine, has been used for disease treatment for many years. The effects of SBT oil on AD mouse model induced by repeated administration of 2,4dinitrochlorobenzene (DNCB) in BALB/c mice was evaluated in this study. Methods: Mice were divided into four groups including the normal control group, AD model group, AD model group treated with SBT oil (5 ml/kg) and AD model group treated with SBT oil (10 ml/kg). Same volume at different concentrations of SBT oil was applied daily on the latter two groups by gavage for 15 days following AD model induction. The function of skin barrier and the production of IL-4, IFN-γ, TNF-α and TSLP were examined after animal sacrifice. The migration and mature of langerhans cell (LCs) in lymph node was further assessed by flow cytometry. Results: SBT oil alleviated dermatitis scores, decreased ear thickness, prevented infiltration of mast cell, reduced lymph node weight and depressed activity of Th2 cells. SBT oil also reduced the expression of IL-4, IFN-γ, TNF-α and TSLP in ear tissue, IgE level in serum and mRNA relative expression of IL-4, IFN-γ, TNF-α in lymph node. Moreover, SBT oil inhibited the migration of LCs cells from local lesions to lymph node and it's mature in lymph node. Conclusions: These results suggest SBT oil had a beneficial effect either systemic or regional on DNCB-induced AD mice via maintain the balance of Th1/Th2 and may be a potential complementary candidate for AD treatment.

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The delivery of mRNA to colon inflammatory lesions by lipid-nano-particles containing environmentally-sensitive lipid-like materials with oleic acid scaffolds

Cited by 22 publications

References 18 publications

Self‐Degradable Lipid‐Like Materials Based on “Hydrolysis accelerated by the intra‐Particle Enrichment of Reactant (HyPER)” for Messenger RNA Delivery

Self‐Degradable Lipid‐Like Materials Based on “Hydrolysis accelerated by the intra‐Particle Enrichment of Reactant (HyPER)” for Messenger RNA Delivery

Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand Adjuvant

Ameliorative effects of sea buckthorn oil on DNCB induced atopic dermatitis model mice via regulation the balance of Th1/Th2

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