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Mitigating Lactate-Associated Immunosuppression against Intracellular Bacteria Using Thermoresponsive Nanoparticles
Shuya Xiao1, Jundan Yi1, Yueting Zhang1
1School of stomatology, Lanzhou University, Lanzhou 730000, People's Republic of China.
Abstract:
Intracellular bacteria are the major contributor to the intractability of septic arthritis, which are sequestered in macrophages to undermine the innate immune response and avoid the antibacterial effect of antibiotics due to the obstruction of the cell membrane. Herein, we report a thermoresponsive nanoparticle, which consists of a phase-change material shell (fatty acids) and an oxygen-producing core (CaO2-vancomycin). Under external thermal stimulation, the shell of the nanoparticle transforms from a solid phase to a liquid phase. Then the CaO2-Vancomycin core is exposed to the surrounding aqueous solution to release vancomycin and generate Ca(OH)2 and oxygen, thereby depleting accumulated lactate to mitigate lactate-associated immunosuppression, stabilizing hypoxia-inducible factor-1α (HIF-1α) to enhance M1-like polarization of macrophages, and increasing reactive oxygen species (ROS) and reactive nitrogen species (RNS) production. This combined effect between the controlled release of antibiotics and enhancement of host innate immunity provides a promising strategy to combat intracellular bacteria for septic arthritis therapy.
Insights
This study introduces a novel thermoresponsive nanoparticle for treating septic arthritis. The nanoparticle releases vancomycin and oxygen, enhancing the immune response against intracellular bacteria.
Area of Science:
- Biomaterials Science
- Immunology
- Infectious Diseases
Background:
- Intracellular bacteria cause difficult-to-treat septic arthritis by hiding in macrophages.
- This sequestration impairs the immune response and antibiotic efficacy due to cell membrane barriers.
Purpose of the Study:
- To develop a thermoresponsive nanoparticle for enhanced septic arthritis therapy.
- To investigate the nanoparticle's ability to combat intracellular bacteria and modulate the host immune response.
Main Methods:
- A thermoresponsive nanoparticle with a fatty acid shell and a calcium peroxide-vancomycin core was synthesized.
- The nanoparticle releases vancomycin and generates oxygen upon thermal stimulation.
- The effects on lactate levels, macrophage polarization, and reactive species production were analyzed.
Main Results:
- The nanoparticle effectively releases vancomycin and produces oxygen.
- Oxygen generation mitigates immunosuppression by depleting lactate.
- The treatment enhances M1-like macrophage polarization and increases reactive oxygen and nitrogen species.
Conclusions:
- The developed nanoparticle offers a dual approach by delivering antibiotics and boosting innate immunity.
- This strategy shows promise for overcoming the challenges of intracellular bacterial infections in septic arthritis.
