Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

Kim, Byungji; Yang, Qinglin; Chan, Leslie W.; Bhatia, Sangeeta N.; Ruoslahti, Erkki; Sailor, Michael J.

doi:10.1039/d0nh00624f

Cited by 21 publications

(18 citation statements)

References 54 publications

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“…Lowgrade inflammation is common in autoimmunity (145), with an inflammatory signature similar to COVID-19 (146). The therapeutic usefulness of IRF5 inhibitors is yet to be determined (13,123,(145)(146)(147)(148)175).…”

Section: Discussionmentioning

confidence: 99%

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

Stoy

2021

Front. Immunol.

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Interleukin-1 receptor-associated kinase 4 (IRAK4) and interferon regulatory factor 5 (IRF5) lie sequentially on a signaling pathway activated by ligands of the IL-1 receptor and/or multiple TLRs located either on plasma or endosomal membranes. Activated IRF5, in conjunction with other synergistic transcription factors, notably NF-κB, is crucially required for the production of proinflammatory cytokines in the innate immune response to microbial infection. The IRAK4-IRF5 axis could therefore have a major role in the induction of the signature cytokines and chemokines of the hyperinflammatory state associated with severe morbidity and mortality in COVID-19. Here a case is made for considering IRAK4 or IRF5 inhibitors as potential therapies for the “cytokine storm” of COVID-19.

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Section: Discussionmentioning

confidence: 99%

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

Stoy

2021

Front. Immunol.

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“…Treatment with AgPd 0.38 nanozymes could significantly reduce the levels of these cytokines and immune-related cells and successfully lowered them close to healthy levels (Figure f–h), indicating the effective immune suppression capability on the inflammatory responses. Kim and co-workers prepared a macrophage-targeting fusogenic porous silicon (F-pSi) nanoparticle system to deliver siRNA against the Irf5 gene of macrophages. , The proinflammatory macrophage marker IRF5 was remarkably knocked down, inhibiting the inflammatory phenotype of macrophages to improve the survival rates of mice whose deep tissues were infected by S. aureus , MRSA, or P. aeruginosa .…”

Section: Nanosystems For Suppressing Excessive Immune Responses Again...mentioning

confidence: 99%

“…Besides, the authors found that the infection induced by P. aeruginosa could increase the serum levels of proinflammatory cytokines and co-workers prepared a macrophage-targeting fusogenic porous silicon (F-pSi) nanoparticle system to deliver siRNA against the Irf5 gene of macrophages. 64,65 The proinflammatory macrophage marker IRF5 was remarkably knocked down, inhibiting the inflammatory phenotype of macrophages to improve the survival rates of mice whose deep tissues were infected by S. aureus, MRSA, or P. aeruginosa.…”

Section: Nanosystems For Suppressing Excessive Immune Responses Again...mentioning

confidence: 99%

Nanosystems for Immune Regulation against Bacterial Infections: A Review

Zhang

Chen

Zhao

2022

ACS Appl. Nano Mater.

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The immune system constitutes the fortifications that safeguard the body against bacterial infections. Artificial nanosystems possess many attractive properties including the ability to modulate the immune responses against bacterial infections. On the one hand, antigen-loaded nanosystems have emerged as a promising alternative to convensional vaccines, protecting the host from infection. On the other hand, immunity can be regulated by nanosystems to treat infections caused by bacteria and related diseases. Herein, we initially introduce the recent advances of artificial nanosystems in the development of different vaccines including subunit and toxoid vaccines. Then, we focus on discussing the employment of nanosystems for the activation of immunity, including innate and adaptive immunity, to treat bacteria-induced infectious diseases. In addition, nanosystems with immunosuppressive capabilities are also highlighted, which can restrain the overactivation of immune responses, thereby relieving inflammation in the face of infections. Finally, we discuss current challenges and provide perspectives for future development in this rapidly growing field. Thus, this review is expected to inspire more advanced research of using nanosystems to achieve immune regulation toward practical applications.

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“…Reverse vaccinology (RV) is an up-to-date approach and is used to identify putative surface-associated proteins without the need to culture the microorganisms [26]. Through immunotherapy, pathogen-specific antibodies can be designed and produced; meanwhile, immunological interventions in the human immune system are trained to tackle bacterial infections by acquiring adaptive immunity [27]. The latter strategy, using vaccines in particular, holds great importance in lowering the burden of AR [28].…”

Section: Introductionmentioning

confidence: 99%

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

et al. 2022

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Antibiotic resistance (AR) is the resistance mechanism pattern in bacteria that evolves over some time, thus protecting the bacteria against antibiotics. AR is due to bacterial evolution to make itself fit to changing environmental conditions in a quest for survival of the fittest. AR has emerged due to the misuse and overuse of antimicrobial drugs, and few antibiotics are now left to deal with these superbug infections. To combat AR, vaccination is an effective method, used either therapeutically or prophylactically. In the current study, an in silico approach was applied for the design of multi-epitope-based vaccines against Providencia rettgeri, a major cause of traveler’s diarrhea. A total of six proteins: fimbrial protein, flagellar hook protein (FlgE), flagellar basal body L-ring protein (FlgH), flagellar hook-basal body complex protein (FliE), flagellar basal body P-ring formation protein (FlgA), and Gram-negative pili assembly chaperone domain proteins, were considered as vaccine targets and were utilized for B- and T-cell epitope prediction. The predicted epitopes were assessed for allergenicity, antigenicity, virulence, toxicity, and solubility. Moreover, filtered epitopes were utilized in multi-epitope vaccine construction. The predicted epitopes were joined with each other through specific GPGPG linkers and were joined with cholera toxin B subunit adjuvant via another EAAAK linker in order to enhance the efficacy of the designed vaccine. Docking studies of the designed vaccine construct were performed with MHC-I (PDB ID: 1I1Y), MHC-II (1KG0), and TLR-4 (4G8A). Findings of the docking study were validated through molecular dynamic simulations, which confirmed that the designed vaccine showed strong interactions with the immune receptors, and that the epitopes were exposed to the host immune system for proper recognition and processing. Additionally, binding free energies were estimated, which highlighted both electrostatic energy and van der Waals forces to make the complexes stable. Briefly, findings of the current study are promising and may help experimental vaccinologists to formulate a novel multi-epitope vaccine against P. rettgeri.

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Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

Abstract: Bacterial infections are re-emerging as substantial threats to global health due to the limited selection of antibiotics that are capable of overcoming antibiotic-resistant strains. By deterring such mutations whilst minimizing...

Cited by 21 publications

References 54 publications

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

Nanosystems for Immune Regulation against Bacterial Infections: A Review

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

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