Prussian blue-decorated indocyanine green-loaded mesoporous silica nanohybrid for synergistic photothermal-photodynamic-chemodynamic therapy against methicillin-resistant Staphylococcus aureus.

Nanomaterial-based synergistic antibacterial agents are considered as promising tools to combat infections caused by antibiotic-resistant bacteria. Herein, multifunctional mesoporous silica nanoparticle (MSN)-based nanocomposites were fabricated for synergistic photothermal/photodynamic/chemodynamic therapy against methicillin-resistant Staphylococcus aureus (MRSA). MSN loaded with indocyanine green (ICG) as a core, while Prussian blue (PB) nanostructure was decorated on MSN surface via in situ growth method to form a core-shell nanohybrid (MSN-ICG@PB). Upon a near infrared (NIR) laser excitation, MSN-ICG@PB (200 µg mL-1) exhibited highly efficient singlet oxygen (1O2) generation and hyperthermia effect (48.7℃). In the presence of exogenous H2O2, PB with peroxidase-like activity promoted the generation of toxic hydroxyl radicals (•OH) to achieve chemodynamic therapy (CDT). PTT can greatly increase the permeability of bacterial lipid membrane, facilitating the generated 1O2 and •OH to kill bacteria more efficiently. Under NIR irradiation and exogenous H2O2, MSN-ICG@PB (200 µg mL-1) with good biocompatibility exhibited a synergistic antibacterial effect against MRSA with high bacterial killing efficiency (>98 %). Moreover, due to the synergistic bactericidal mechanism, MSN-ICG@PB with satisfactory biosafety makes it a promising antimicrobial agent to fight against MRSA.

Epigallocatechin-3-gallate derived polymer coated Prussian blue for synergistic ROS elimination and antibacterial therapy.

Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core-shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.