Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections
| Autor: | Qinglin Yang, Leslie W. Chan, Michael J. Sailor, Sangeeta N. Bhatia, Byungji Kim, Erkki Ruoslahti |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Methicillin-Resistant Staphylococcus aureus 0301 basic medicine Silicon medicine.drug_class medicine.medical_treatment 030106 microbiology Antibiotics medicine.disease_cause Article Microbiology 03 medical and health sciences Immune system In vivo Pneumonia Staphylococcal medicine Animals Gene silencing General Materials Science RNA Small Interfering Lung Drug Carriers Mice Inbred BALB C business.industry Pseudomonas aeruginosa Macrophages Muscles Immunotherapy 030104 developmental biology Staphylococcus aureus Interferon Regulatory Factors Nanoparticles business Porosity IRF5 |
| Zdroj: | Nanoscale Horiz |
| ISSN: | 2055-6764 2055-6756 |
| Popis: | 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 the need to develop new pathogen-specific antibiotics, immunotherapy offers a broad-spectrum therapeutic solution against bacterial infections. In particular, pathology resulting from excessive immune response (i.e. fibrosis, necrosis, exudation, breath impediment) contributes significantly to negative disease outcome. Herein, we present a nanoparticle that is targeted to activated macrophages and loaded with siRNA against the Irf5 gene. This formulation is able to induce >80% gene silencing in activated macrophages in vivo, and it inhibits the excessive inflammatory response, generating a significantly improved therapeutic outcome in mouse models of bacterial infection. The versatility of the approach is demonstrated using mice with antibiotic-resistant Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) muscle and lung infections, respectively. Effective depletion of the Irf5 gene in macrophages is found to significantly improve the therapeutic outcome of infected mice, regardless of the bacteria strain and type. |
| Databáze: | OpenAIRE |
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