pH-Responsive Hyperbranched Polymer Nanoparticles to Combat Intracellular Infection by Disrupting Bacterial Wall and...

Area of Science:

• Biomaterials Science
• Immunology
• Infectious Diseases

Background:

• Intracellular bacterial infections are a significant public health concern.
• Macrophages are crucial immune cells, but bacteria can evade their antimicrobial functions.
• Developing strategies to overcome bacterial evasion within macrophages is essential.

Purpose of the Study:

• To develop dual pH-responsive polymer nanoparticles (PCA) for treating intracellular bacterial infections.
• To investigate PCA's ability to activate macrophages and directly eliminate bacteria.
• To evaluate PCA's efficacy in promoting bacteria-infected wound healing.

Main Methods:

• Synthesis of dual pH-responsive poly[(3-phenylprop-2-ene-1,1-diyl)bis(oxy)bis(enthane-2,1-diyl)diacrylate-co-N-aminoethylpiperazine] (PCA) nanoparticles.
• Assessment of PCA's pH-responsive properties, including charge alteration and cinnamaldehyde release.
• Evaluation of PCA's antibacterial activity, macrophage uptake, ROS generation, and M1 polarization.
• In vivo studies on bacteria-infected wound healing models.

Main Results:

• PCA nanoparticles exhibit dual pH-responsive behavior, increasing positive charge and releasing cinnamaldehyde in acidic conditions.
• PCA nanoparticles effectively inhibit bacterial growth by damaging bacterial walls.
• PCA nanoparticles are internalized by macrophages, stimulating reactive oxygen species (ROS) production and upregulating M1 polarization.
• PCA treatment significantly promotes wound healing in vivo.

Conclusions:

• Dual pH-responsive PCA nanoparticles offer a dual-action therapeutic strategy against intracellular bacteria.
• PCA nanoparticles enhance macrophage antimicrobial activity through ROS generation and M1 polarization.
• PCA nanoparticles demonstrate potential for treating intracellular infections and accelerating wound healing.