Modular core-shell polymeric nanoparticles mimicking viral structures for vaccination

Lou, Bo; Beuckelaer, Alain De; Boonstra, Eger; Li, Dandan; Geest, Bruno G. De; Koker, Stefaan De; Mastrobattista, Enrico; Hennink, Wim E.

doi:10.1016/j.jconrel.2018.11.006

Cited by 27 publications

(21 citation statements)

References 62 publications

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“…Emerging evidence suggests that TLRs play fundamental roles in brain development and homeostasis [28, 35, 36]. TLR7 is widely expressed in immune cells, intestinal cells, lung cells, and neural cells, wherein it is also able to detect and respond to specific viral RNAs, single-stranded oligoribonucleotides, siRNAs, and microRNAs, leading to intracellular signaling pathway activation and cytokine production [10, 11, 19, 37]. In various forms of non-infectious CNS injury, TLR7 also serves as a prominent mediator of neurodegeneration [11, 14, 38].…”

Section: Discussionmentioning

confidence: 99%

EV71 infection induces neurodegeneration via activating TLR7 signaling and IL-6 production

Luo

Wang

et al. 2019

PLoS Pathog

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As a neurotropic virus, human Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease (HFMD) and may develop severe neurological disorders in infants. Toll-like receptor 7 (TLR7) acts as an innate immune receptor and is also a death receptor in the central nervous system (CNS). However, the mechanisms underlying the regulation of TLR7-mediated brain pathogenesis upon EV71 infection remain largely elusive. Here we reveal a novel mechanism by which EV71 infects astrocytes in the brain and induces neural pathogenesis via TLR7 and interleukin-6 (IL-6) in C57BL/6 mice and in human astroglioma U251 cells. Upon EV71 infection, wild-type (WT) mice displayed more significant body weight loss, higher clinical scores, and lower survival rates as compared with TLR7-/- mice. In the cerebral cortex of EV71-infected mice, neurofilament integrity was disrupted, and inflammatory cell infiltration and neurodegeneration were induced in WT mice, whereas these were largely absent in TLR7-/- mice. Similarly, IL-6 production, Caspase-3 cleavage, and cell apoptosis were significantly higher in EV71-infected WT mice as compared with TLR7-/- mice. Moreover, EV71 preferentially infected and induced IL-6 in astrocytes of mice brain. In U251 cells, EV71-induced IL-6 production and cell apoptosis were suppressed by shRNA-mediated knockdown of TLR7 (shTLR7). Moreover, in the cerebral cortex of EV71-infected mice, the blockade of IL-6 with anti-IL-6 antibody (IL-6-Ab) restored the body weight loss, attenuated clinical scores, improved survival rates, reduced the disruption of neurofilament integrity, decreased cell apoptotic induction, and lowered levels of Caspase-3 cleavage. Similarly, in EV71-infected U251 cells, IL-6-Ab blocked EV71-induced IL-6 production and cell apoptosis in response to viral infection. Collectively, it’s exhibited TLR7 upregulation, IL-6 induction and astrocytic cell apoptosis in EV71-infected human brain. Taken together, we propose that EV71 infects astrocytes of the cerebral cortex in mice and human and triggers TLR7 signaling and IL-6 release, subsequently inducing neural pathogenesis in the brain.

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Section: Discussionmentioning

confidence: 99%

EV71 infection induces neurodegeneration via activating TLR7 signaling and IL-6 production

Luo

Wang

et al. 2019

PLoS Pathog

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“…P19 was prepared from New England Bio Labs Inc and used without further purification. P19 siRNA Binding Protein (10 units/ml) was stored at −20 °C 16 . Screen-printed carbon electrode modified with gold nanoparticles on the ceramic substrate was purchased from DropSens Inc.…”

Section: Methodsmentioning

confidence: 99%

“…So, 6 mg/ml RNA probe and 3 mg/ml miR21 were blended in a vial containing Tris-EDTA Buffer (TEB). The target was put into the thermal shaker which was set to 65 °C and 250 rpm mixing speed and kept there for 1 h 16 . Then, 1 mM of 2 ml hybrid of miR21 was added on the surface of the electrode and incubated at 37 °C for 2 h in a dark without shaking.…”

Section: Methodsmentioning

confidence: 99%

“…DPV and EIS techniques were used for monitoring the electrochemical reactions in PBS buffer (pH 7.4) in the presence of the [Fe(CN) 6 ] −3/−4 redox couple. To evaluation the sensitivity of miR, increasing concentrations (1 a.M to 500 p.M) of miR21, were incubated with 1 μM of RNA probe in a 100 μL total volume of PBS at 37 °C for 1 h after incubation of 10 μL of the reaction mixture with cuco 2 o 4 /p19 sensor for 1 h at room temperature, and then washing 3 times with 500 μL of phosphate buffer (PB) and electrochemical reactions were done 16 . To examine the effect of the amount of p19 in limit of detection of 21miR, we dropped 0.4 µl of p19 on the sensor with the increasing concentrations (1 a.M to 500 p.M) as the same of conditions.…”

Section: Identification Of the Specificity And Sensitivity Of The Cucmentioning

confidence: 99%

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Impediometric Electrochemical Sensor Based on The Inspiration of Carnation Italian Ringspot Virus Structure to Detect an Attommolar of miR

Ghazizadeh

Moosavifard

Daneshmand

et al. 2020

Sci Rep

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electrochemical sensors are the tools to detect the accurate and sensitive miRs. there is the challenge to increase the power and sensitivity of the surface for the electrochemical sensor. We design a viruslike hallow structure of cuco 2 o 4 that it holds the large amounts of p19 protein by mimicking of inherent virus (Carnation italian ringspot virus) to detect 21mir with the limit of detection (LOD = 1aM). The electrochemical measurements are performed between the potentials at −0.3 V and +0.3 V with 1 mM [fe(cn) 6 ] −3/−4. After dropping the cuco 2 o 4 on the Scpe (screen carbon printed electrode), the sensor is turned on due to the high electrochemical properties. Then, p19 proteins move into the hallow structure and inhibit the exchange of electrochemical reactions between the shells and the sensor is turned off. Then, adding the duplexes of RNA/miRs cause to increase the electrochemical property of p19 due to the change of p19 conformation and the system is turned on, again. So, for the first time, a virus-like hallow structure has been used to detect the 21miR in the human serum, MCF-7, Hella cells, with high sensitivity, specificity, and reproducibility in few minutes.

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“…One of the systems of nanometric size studied for vaccination has been polymeric nanocapsules. This kind of system has the advantage of having dimensions similar to most pathogens, it can be efficiently processed by the immune system, and therefore can lead to a potent immune response [10,11]. Several raw materials have been studied as coronas in the polymeric nanocapsules developed, including proteins, polypeptides, polyaminoacids and others which have shown the capacity to deliver and control the release of encapsulated molecules, as well as increasing formulation stability in physiological conditions [12].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid Nanocapsules as a Platform for Needle-Free Vaccination

2019

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Vaccination faces many challenges nowadays, and among them the use of adjuvant molecules and needle-free administration are some of the most demanding. The combination of transcutaneous vaccination and nanomedicine through a rationally designed new-formulation could be the solution to this problem. This study focuses on this rational design. For this purpose, new hyaluronic acid nanocapsules (HA-NCs) have been developed. This new formulation has an oily nucleus with immunoadjuvant properties (due to α tocopherol) and a shell made of hyaluronic acid (HA) and decorated with ovalbumin (OVA) as the model antigen. The resulting nanocapsules are smaller than 100 nm, have a negative superficial charge and have a population that is homogeneously distributed. The systems show high colloidal stability in storage and physiological conditions and high OVA association without losing their integrity. The elevated interaction of the novel formulation with the immune system was demonstrated through complement activation and macrophage viability studies. Ex vivo studies using a pig skin model show the ability of these novel nanocapsules to penetrate and retain OVA in higher quantities in skin when compared to this antigen in the control solution. Due to these findings, HA-NCs are an interesting platform for needle-free vaccination.

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Modular core-shell polymeric nanoparticles mimicking viral structures for vaccination

Cited by 27 publications

References 62 publications

EV71 infection induces neurodegeneration via activating TLR7 signaling and IL-6 production

EV71 infection induces neurodegeneration via activating TLR7 signaling and IL-6 production

Impediometric Electrochemical Sensor Based on The Inspiration of Carnation Italian Ringspot Virus Structure to Detect an Attommolar of miR

Hyaluronic Acid Nanocapsules as a Platform for Needle-Free Vaccination

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