Related Experiment Video

Updated: Mar 19, 2026

Evaluating the Immune Response of a Nanoemulsion Adjuvant Vaccine Against Methicillin-Resistant Staphylococcus aureus MRSA Infection

Evaluating the Immune Response of a Nanoemulsion Adjuvant Vaccine Against Methicillin-Resistant Staphylococcus aureus MRSA Infection

Published on: September 1, 2023

An Inorganic Stimulator of Interferon Genes Sensitizer for the Metalloimmunotherapy of Intracellular Bacterial

Chuang Yang¹, Nannan Zheng², Yao Luo¹

¹Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.

|March 17, 2026

Abstract:

Bone infections associated with the formation of intracellular bacterial niches in macrophages and bone cells play an important role in the long-lasting nature of chronic infections. One major mechanism of intracellular bacterial persistence lies in the low antibiotic permeability and subverted immune responses. It is now increasingly apparent that metal elements such as Mn, Zn, and Se exploit the stimulator of interferon genes (STING) pathway in immune cells to combat invading pathogens and intrinsic aberrant cells. Here, we report a prototype of bacterial metalloimmunotherapy using a synthetic inorganic STING sensitizer (SSZ), which comprises Se-loaded mesoporous silica nanoparticles and ZnO quantum dot lids. Mechanistically, the inorganic STING sensitizer could restore the bactericidal activity of lysosomes in macrophages and generate type I interferons, achieving effective intracellular bacterial clearance. Topical application of the inorganic STING sensitizer initiated robust antibacterial immunity, leading to obvious therapeutic efficacy toward both intracellular bacteria and biofilms in a mouse osteomyelitis model. Rechallenging the SSZ-cured mice with bacteria led to effective inhibition of bacterial growth, suggesting the generation of long-term antibacterial memory responses. This antibacterial strategy was also proven effective in a rabbit knee prosthetic infection model. Overall, the inorganic STING sensitizer offers an alternative approach for intracellular bacterial treatments, and this underscores the great potential of metalloimmunotherapy for infectious diseases.

Insights

This study introduces a novel inorganic STING sensitizer (SSZ) for treating chronic bone infections. SSZ effectively clears intracellular bacteria by restoring immune cell function and generating long-term antibacterial memory.

Area of Science:

Immunology
Nanotechnology
Infectious Diseases

Background:

Chronic bone infections persist due to intracellular bacterial niches within macrophages and bone cells.
Low antibiotic penetration and suppressed immune responses contribute to bacterial persistence.
Metal elements like manganese (Mn), zinc (Zn), and selenium (Se) can modulate the stimulator of interferon genes (STING) pathway for pathogen defense.

Purpose of the Study:

To develop and evaluate a synthetic inorganic STING sensitizer (SSZ) for treating intracellular bacterial infections.
To investigate the mechanism of action of SSZ in restoring immune cell bactericidal activity.
To assess the therapeutic efficacy of SSZ in preclinical models of osteomyelitis and prosthetic joint infections.

Main Methods:

A synthetic inorganic STING sensitizer (SSZ) was designed using Se-loaded mesoporous silica nanoparticles and ZnO quantum dot lids.
The SSZ's mechanism involved restoring lysosomal bactericidal activity and inducing type I interferons in macrophages.
Efficacy was tested in mouse osteomyelitis and rabbit prosthetic joint infection models, including biofilm eradication and assessment of long-term immune memory.

Main Results:

The SSZ effectively cleared intracellular bacteria by restoring macrophage bactericidal function and promoting type I interferon production.
Topical application of SSZ demonstrated significant therapeutic efficacy against intracellular bacteria and biofilms in a mouse osteomyelitis model.
SSZ-treated mice exhibited inhibited bacterial regrowth upon re-challenge, indicating the development of long-term antibacterial memory responses.
The antibacterial strategy proved effective in a rabbit prosthetic joint infection model.

Conclusions:

The inorganic STING sensitizer (SSZ) represents a promising metalloimmunotherapy approach for intracellular bacterial infections.
SSZ restores immune cell function to combat persistent bacterial infections, offering an alternative to conventional antibiotics.
This study highlights the potential of metalloimmunotherapy for treating challenging infectious diseases, including chronic bone infections.

Read full analysis

Keywords:

STING sensitizer biofilm immunotherapy implant infection intracellular bacteria

More Related Videos

In Vitro Cellular Activity Evaluation of the Nanoemulsion Vaccine Adjuvant Ophiopogonin D

In Vitro Cellular Activity Evaluation of the Nanoemulsion Vaccine Adjuvant Ophiopogonin D

Published on: December 9, 2022

Vascular Gene Transfer from Metallic Stent Surfaces Using Adenoviral Vectors Tethered through Hydrolysable Cross-linkers

Vascular Gene Transfer from Metallic Stent Surfaces Using Adenoviral Vectors Tethered through Hydrolysable Cross-linkers

Published on: August 12, 2014

Related Concept Videos

Inhibitors of Viral Protein Synthesis

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...

Antimicrobial Proteins

Antimicrobial Proteins

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...

Microorganisms in Medicine and Therapeutics

Microorganisms in Medicine and Therapeutics

Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.

Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

Antigens Involved in Adaptive Immunity

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...

Articles linked to this work by shared authors, journal, and citation graph.

The E2 ubiquitin-conjugating enzymes OsUBC11 and OsUBC12 promote rice seed germination by ubiquitinating and destabilizing OsABI3 in the ABA signaling pathway.

The Plant journal : for cell and molecular biology·2026

Multifunctional Nanofiber Membrane With Directional Moisture Pumping, Rapid Cooling, and Antibacterial Activity for Intertrigo Wound Microclimate Regulation and Therapy.

Advanced healthcare materials·2026

Annotated dataset for surface defect detection on ceramic substrates in manufacturing.

Data in brief·2026

eGDR and gastrointestinal cancer mortality in the UK Biobank: a prospective cohort study.

BMC cancer·2026

Early life sugar rationing and ageing related diseases, biological ageing and mortality.

Nature communications·2026

A Low-Power PLL-Less Wideband OOK Wireless Neural-Signal Transmitter for Miniaturized Neural Interfaces with In Vivo Validation in Freely Moving Mice.

Biosensors·2026

See all related articles