International Journal of Molecular Sciences

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7 pages, 234 KiB

Open AccessEditorial

Nanoparticles and Other Nanostructures and the Control of Pathogens: From Bench to Vaccines

by Ariane Boudier and Alain Le Faou

Int. J. Mol. Sci. 2023, 24(10), 9063; https://doi.org/10.3390/ijms24109063 - 21 May 2023

Cited by 2 | Viewed by 1445

Abstract

Parasites and microorganisms (protozoa, bacteria, and viruses) are still a concern despite progress in hygiene and anti-infectious therapy [...] Full article

(This article belongs to the Special Issue Nanoparticles and Other Nanostructures and the Control of Pathogens: From Bench to Vaccines)

Research

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15 pages, 3758 KiB

Open AccessArticle

Exploring the Role of GMMA Components in the Immunogenicity of a 4-Valent Vaccine against Shigella

by Francesca Mancini, Renzo Alfini, Valentina Caradonna, Valentina Monaci, Martina Carducci, Gianmarco Gasperini, Diego Piccioli, Massimiliano Biagini, Carlo Giannelli, Omar Rossi, Mariagrazia Pizza and Francesca Micoli

Int. J. Mol. Sci. 2023, 24(3), 2742; https://doi.org/10.3390/ijms24032742 - 1 Feb 2023

Cited by 8 | Viewed by 2707

Abstract

Shigellosis is the leading cause of diarrheal disease, especially in children of low- and middle-income countries, and is often associated with anti-microbial resistance. Currently, there are no licensed vaccines widely available against Shigella, but several candidates based on the O-antigen (OAg) portion [...] Read more.

Shigellosis is the leading cause of diarrheal disease, especially in children of low- and middle-income countries, and is often associated with anti-microbial resistance. Currently, there are no licensed vaccines widely available against Shigella, but several candidates based on the O-antigen (OAg) portion of lipopolysaccharides are in development. We have proposed Generalized Modules for Membrane Antigens (GMMA) as an innovative delivery system for OAg, and a quadrivalent vaccine candidate containing GMMA from S. sonnei and three prevalent S. flexneri serotypes (1b, 2a and 3a) is moving to a phase II clinical trial, with the aim to elicit broad protection against Shigella. GMMA are able to induce anti-OAg-specific functional IgG responses in animal models and healthy adults. We have previously demonstrated that antibodies against protein antigens are also generated upon immunization with S. sonnei GMMA. In this work, we show that a quadrivalent Shigella GMMA-based vaccine is able to promote a humoral response against OAg and proteins of all GMMA types contained in the investigational vaccine. Proteins contained in GMMA provide T cell help as GMMA elicit a stronger anti-OAg IgG response in wild type than in T cell-deficient mice. Additionally, we observed that only the trigger of Toll-like Receptor (TLR) 4 and not of TLR2 contributed to GMMA immunogenicity. In conclusion, when tested in mice, GMMA of a quadrivalent Shigella vaccine candidate combine both adjuvant and carrier activities which allow an increase in the low immunogenic properties of carbohydrate antigens. Full article

(This article belongs to the Special Issue Nanoparticles and Other Nanostructures and the Control of Pathogens: From Bench to Vaccines)

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14 pages, 2007 KiB

Open AccessArticle

Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines

by Claire Monge, Camille Ayad, Anne-Lise Paris, Renaud Rovera, Evelyne Colomb and Bernard Verrier

Int. J. Mol. Sci. 2022, 23(21), 13440; https://doi.org/10.3390/ijms232113440 - 3 Nov 2022

Cited by 4 | Viewed by 2524

Abstract

Among mucosal administration routes for vaccines, the sublingual route has been proven capable of inducing a potent systemic and mucosal immune response. However, the absence of a simple and compliant delivery system and the lack of robust mucosal adjuvants impede the development of [...] Read more.

Among mucosal administration routes for vaccines, the sublingual route has been proven capable of inducing a potent systemic and mucosal immune response. However, the absence of a simple and compliant delivery system and the lack of robust mucosal adjuvants impede the development of sublingual vaccines. Here, we describe a mucoadhesive patch made of a layer-by-layer assembly of polysaccharides, chitosan, and hyaluronic acid. The mucoadhesive patch was covered by adjuvanted nanoparticles carrying viral proteins. We showed that the nanoparticles effectively cross the outer layers of the sublingual mucosa to reach the epithelium. Furthermore, the encapsulated adjuvants, 3M-052 and mifamurtide, targeting toll-like receptor (TLR) 7/8 and nucleotide-binding oligomerization domain-2 (NOD2), respectively, remain fully active after encapsulation into nanoparticles and exhibit a cytokine/chemokine signature similar to the mucosal gold-standard adjuvant, the cholera toxin. However, the particulate adjuvants induced more moderate levels of proinflammatory interleukin (IL)-6 and keratinocyte chemoattractant (KC), suggesting a controlled activation of the innate immune response. Full article

(This article belongs to the Special Issue Nanoparticles and Other Nanostructures and the Control of Pathogens: From Bench to Vaccines)

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16 pages, 5594 KiB

Open AccessArticle

Anti-HSV Activity of Metallic Nanoparticles Functionalized with Sulfonates vs. Polyphenols

by Emilia Tomaszewska, Katarzyna Ranoszek-Soliwoda, Katarzyna Bednarczyk, Agnieszka Lech, Martyna Janicka, Marcin Chodkowski, Maciej Psarski, Grzegorz Celichowski, Malgorzata Krzyzowska and Jarosław Grobelny

Int. J. Mol. Sci. 2022, 23(21), 13104; https://doi.org/10.3390/ijms232113104 - 28 Oct 2022

Cited by 8 | Viewed by 1825

Abstract

Metallic nanoparticles exhibit broad-spectrum activity against bacteria, fungi, and viruses. The antiviral activity of nanoparticles results from the multivalent interactions of nanoparticles with viral surface components, which result from the nanometer size of the material and the presence of functional compounds adsorbed on [...] Read more.

Metallic nanoparticles exhibit broad-spectrum activity against bacteria, fungi, and viruses. The antiviral activity of nanoparticles results from the multivalent interactions of nanoparticles with viral surface components, which result from the nanometer size of the material and the presence of functional compounds adsorbed on the nanomaterial surface. A critical step in the virus infection process is docking and entry of the virus into the host cell. This stage of the infection can be influenced by functional nanomaterials that exhibit high affinity to the virus surface and hence can disrupt the infection process. The affinity of the virus to the nanomaterial surface can be tuned by the specific surface functionalization of the nanomaterial. The main purpose of this work was to determine the influence of the ligand type present on nanomaterial on the antiviral properties against herpes simplex virus type 1 and 2. We investigated the metallic nanoparticles (gold and silver) with different sizes (5 nm and 30 nm), coated either with polyphenol (tannic acid) or sulfonates (ligands with terminated sulfonate groups). We found that the antiviral activity of nano-conjugates depends significantly on the ligand type present on the nanoparticle surface. Full article

(This article belongs to the Special Issue Nanoparticles and Other Nanostructures and the Control of Pathogens: From Bench to Vaccines)

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13 pages, 6477 KiB

Open AccessArticle

Imaging the Infection Cycle of T7 at the Single Virion Level

by Bálint Kiss, Luca Annamária Kiss, Zsombor Dávid Lohinai, Dorottya Mudra, Hedvig Tordai, Levente Herenyi, Gabriella Csík and Miklós Kellermayer

Int. J. Mol. Sci. 2022, 23(19), 11252; https://doi.org/10.3390/ijms231911252 - 24 Sep 2022

Cited by 2 | Viewed by 2183

Abstract

T7 phages are E. coli-infecting viruses that find and invade their target with high specificity and efficiency. The exact molecular mechanisms of the T7 infection cycle are yet unclear. As the infection involves mechanical events, single-particle methods are to be employed to [...] Read more.

T7 phages are E. coli-infecting viruses that find and invade their target with high specificity and efficiency. The exact molecular mechanisms of the T7 infection cycle are yet unclear. As the infection involves mechanical events, single-particle methods are to be employed to alleviate the problems of ensemble averaging. Here we used TIRF microscopy to uncover the spatial dynamics of the target recognition and binding by individual T7 phage particles. In the initial phase, T7 virions bound reversibly to the bacterial membrane via two-dimensional diffusive exploration. Stable bacteriophage anchoring was achieved by tail-fiber complex to receptor binding which could be observed in detail by atomic force microscopy (AFM) under aqueous buffer conditions. The six anchored fibers of a given T7 phage-displayed isotropic spatial orientation. The viral infection led to the onset of an irreversible structural program in the host which occurred in three distinct steps. First, bacterial cell surface roughness, as monitored by AFM, increased progressively. Second, membrane blebs formed on the minute time scale (average ~5 min) as observed by phase-contrast microscopy. Finally, the host cell was lysed in a violent and explosive process that was followed by the quick release and dispersion of the phage progeny. DNA ejection from T7 could be evoked in vitro by photothermal excitation, which revealed that genome release is mechanically controlled to prevent premature delivery of host-lysis genes. The single-particle approach employed here thus provided an unprecedented insight into the details of the complete viral cycle. Full article

(This article belongs to the Special Issue Nanoparticles and Other Nanostructures and the Control of Pathogens: From Bench to Vaccines)

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29 pages, 7780 KiB

Open AccessArticle

In Vivo Evaluation of Praziquantel-Loaded Solid Lipid Nanoparticles against S. mansoni Infection in Preclinical Murine Models

by Tayo A. Adekiya, Pradeep Kumar, Pierre P. D. Kondiah, Philemon Ubanako and Yahya E. Choonara

Int. J. Mol. Sci. 2022, 23(16), 9485; https://doi.org/10.3390/ijms23169485 - 22 Aug 2022

Cited by 6 | Viewed by 2401

Abstract

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim [...] Read more.

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs’ suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in S. mansoni-infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis. Full article

(This article belongs to the Special Issue Nanoparticles and Other Nanostructures and the Control of Pathogens: From Bench to Vaccines)

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16 pages, 3367 KiB

Open AccessArticle

The Impact of Multiple Functional Layers in the Structure of Magnetic Nanoparticles and Their Influence on Albumin Interaction

by Joana C. Pieretti, Jordan Beurton, Julián Munevar, Luiz C. C. M. Nagamine, Alain Le Faou, Amedea B. Seabra, Igor Clarot and Ariane Boudier

Int. J. Mol. Sci. 2021, 22(19), 10477; https://doi.org/10.3390/ijms221910477 - 28 Sep 2021

Cited by 5 | Viewed by 2068

Abstract

In nanomedicine, hybrid nanomaterials stand out for providing new insights in both the diagnosis and treatment of several diseases. Once administered, engineered nanoparticles (NPs) interact with biological molecules, and the nature of this interaction might directly interfere with the biological fate and action [...] Read more.

In nanomedicine, hybrid nanomaterials stand out for providing new insights in both the diagnosis and treatment of several diseases. Once administered, engineered nanoparticles (NPs) interact with biological molecules, and the nature of this interaction might directly interfere with the biological fate and action of the NPs. In this work, we synthesized a hybrid magnetic nanostructure, with antibacterial and antitumoral potential applications, composed of a magnetite core covered by silver NPs, and coated with a modified chitosan polymer. As magnetite NPs readily oxidize to maghemite, we investigated the structural properties of the NPs after addition of the two successive layers using Mössbauer spectroscopy. Then, the structural characteristics of the NPs were correlated to their interaction with albumin, the major blood protein, to evidence the consequences of its binding on NP properties and protein retention. Thermodynamic parameters of the NPs–albumin interaction were determined. We observed that the more stable NPs (coated with modified chitosan) present a lower affinity for albumin in comparison to pure magnetite and magnetite/silver hybrid NPs. Surface properties were key players at the NP–biological interface. To the best of our knowledge, this is the first study that demonstrates a correlation between the structural properties of complex hybrid NPs and their interaction with albumin. Full article

(This article belongs to the Special Issue Nanoparticles and Other Nanostructures and the Control of Pathogens: From Bench to Vaccines)

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Review

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14 pages, 1117 KiB

Open AccessReview

Biological Functions and Applications of Virus-Related Bacterial Nanoparticles: A Review

by Toshiki Nagakubo

Int. J. Mol. Sci. 2022, 23(5), 2595; https://doi.org/10.3390/ijms23052595 - 26 Feb 2022

Cited by 4 | Viewed by 3157

Abstract

Accumulating evidence suggests that microorganisms produce various nanoparticles that exhibit a variety of biological functions. The structure of these bacterial nanoparticles ranges from membrane vesicles composed of membrane lipids to multicomponent proteinaceous machines. Of bacterial nanoparticles, bacterial phage tail-like nanoparticles, associated with virus-related [...] Read more.

Accumulating evidence suggests that microorganisms produce various nanoparticles that exhibit a variety of biological functions. The structure of these bacterial nanoparticles ranges from membrane vesicles composed of membrane lipids to multicomponent proteinaceous machines. Of bacterial nanoparticles, bacterial phage tail-like nanoparticles, associated with virus-related genes, are found in bacteria from various environments and have diverse functions. Extracellular contractile injection systems (eCISs), a type of bacterial phage tail-like nanostructure, have diverse biological functions that mediate the interactions between the producer bacteria and target eukaryote. Known gram-negative bacterial eCISs can act as protein translocation systems and inject effector proteins that modulate eukaryotic cellular processes by attaching to the target cells. Further investigation of the functions of eCISs will facilitate the application of these nanomachines as nano-sized syringes in the field of nanomedicine and vaccine development. This review summarises the recent progress in elucidating the structures and biological functions of nanoparticles that resemble the tail components of phages that infect bacteria and discusses directions for future research to improve the clinical applicability of virus-related bacterial nanoparticles. Full article

(This article belongs to the Special Issue Nanoparticles and Other Nanostructures and the Control of Pathogens: From Bench to Vaccines)

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