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Targeting and arginine-driven synergizing photodynamic therapy with nutritional immunotherapy nanosystems for
Aoxue Zhang1, Hao Wu2, Xin Chen1
1National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Abstract:
The resistance and immune escape of methicillin-resistant Staphylococcus aureus (MRSA) biofilms cause recalcitrant infections. Here, we design a targeting and synergizing cascade PDT with nutritional immunotherapy nanosystems (Arg-PCN@Gel) containing PCN-224 as PDT platform for providing reactive oxygen species (ROS), incorporating arginine (Arg) as nitric oxide (NO) donor to cascade with ROS to produce more lethal ONOO- and promote immune response, and coating with gelatin as targeting agent and persistent Arg provider. The nanosystems adhered to the autolysin of MRSA and inhibited Arg metabolism by down-regulating icdA and icaA. It suppressed polysaccharide intercellular adhesin and extracellular DNA synthesis to prevent biofilm formation. The NO broke mature biofilms and helped ROS and ONOO- penetrate into biofilms to inactivate internal MRSA. Arg-PCN@Gel drove Arg to enhance immunity via inducible NO synthase/NO axis and arginase/polyamine axis and achieve efficient target treatment in MRSA biofilm infections. The targeting and cascading PDT synergized with nutritional immunotherapy provide an effective promising strategy for biofilm-associated infections.
Insights
This study introduces a novel nanosystem (Arg-PCN@Gel) that combines photodynamic therapy (PDT) with nutritional immunotherapy to combat difficult methicillin-resistant Staphylococcus aureus (MRSA) infections. The nanosystem effectively targets and eradicates MRSA biofilms while boosting the immune system.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Nanotechnology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) biofilms are a major cause of persistent infections due to their resistance and immune evasion.
- Current treatments often struggle to penetrate and eradicate mature MRSA biofilms effectively.
Purpose of the Study:
- To develop a novel nanosystem (Arg-PCN@Gel) for targeting and synergizing photodynamic therapy (PDT) with nutritional immunotherapy against MRSA biofilms.
- To investigate the mechanism of action of the nanosystem in inhibiting MRSA biofilm formation and promoting immune response.
Main Methods:
- Design of Arg-PCN@Gel nanosystems incorporating PCN-224 for ROS generation and arginine (Arg) as a nitric oxide (NO) donor, coated with gelatin for targeting.
- Evaluation of nanosystem adherence to MRSA, inhibition of Arg metabolism (down-regulating icdA and icaA), and suppression of biofilm components (polysaccharide intercellular adhesin and extracellular DNA).
- Assessment of NO-mediated biofilm disruption and enhanced ROS/peroxynitrite (ONOO-) penetration for MRSA inactivation, alongside immune system enhancement via inducible NO synthase/NO and arginase/polyamine pathways.
Main Results:
- The Arg-PCN@Gel nanosystems effectively adhered to MRSA and inhibited biofilm formation by down-regulating key metabolic genes.
- Nitric oxide (NO) from the nanosystem disrupted mature biofilms, facilitating the penetration of reactive oxygen species (ROS) and ONOO- to kill internal MRSA.
- The nanosystem successfully enhanced host immunity through specific molecular pathways, leading to efficient targeted treatment of MRSA biofilm infections.
Conclusions:
- The developed Arg-PCN@Gel nanosystem represents a promising strategy for treating recalcitrant MRSA biofilm infections.
- The synergistic combination of targeted PDT and nutritional immunotherapy offers an effective approach to combat biofilm-associated pathogens.
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