Spatiotemporal Release of Reactive Oxygen Species and NO for Overcoming Biofilm Heterogeneity

Abstract

The heterogeneity in biofilms is a major challenge in biofilm therapies due to different susceptibility of bacteria and extracellular polymeric substances (EPS) to antibacterial agents. Here, we describe a therapeutic strategy that overcame biofilm heterogeneity, where antibacterial agent (NO) and EPS dispersant (reactive oxygen species (ROS)‐inducing Fe3+) were separately loaded in the yolk and shell compartment of a yolk–shell nanoplatform. Compared with traditional combinational chemotherapies which suffer from inconsistent pharmacokinetics profiles, this strategy drew on the pharmacokinetic complementarity of ROS and NO, where ROS with a short diffusion distance and a high redox potential corrupted the EPS, facilitating NO, which has a long diffusion distance and a broad antimicrobial spectrum, to penetrate the biofilm and eliminate the resident bacteria. Additionally, the construction of a three‐dimensional spherical biofilm model is novel and clinically relevant.

Amphiphilic Nano-Swords for Direct Penetration and Eradication of Pathogenic Bacterial Biofilms

“…Compounds were then added (in triplicate) to the wells in the first row of the microtiter plate and then serially diluted. The plate was incubated at 37 °C for a minimum of 24 CFU/mL) of GFP-Sa was added to PBS with 4% sheep red blood cells (RBCs). The cells treated with 3a were incubated at 37 °C and 220 rpm for 16−20 h. Bacterial load was determined through plating a 5 μL aliquot with a series of 10-fold dilution onto agar plates and CFUs were counted after 10 h incubation at 37 °C.…”

“…Current anti-biofilm strategies, such as targeting EPS chemical components for integrity compromise, inhibiting EPS synthesis and secretion, and interfering with metabolic activity or direct killing of dormant cells, offer some clinical promise for biofilm inhibition . However, eradication of established biofilms remains a challenge and thus attracts much research interest. − This is presumably because the agents’ penetration into the amphiphilic EPS is highly restricted. Therefore, development of an anti-biofilm agent with high biofilm permeability by targeting the densely packed and amphiphilic structure of EPS is in urgent demand.…”

A dual-modal ROS generator based on multifunctional PDA–MnO2@Ce6 nanozymes for synergistic chemo-photodynamic antibacterial therapy

“…In addition, extracellular polymeric substances (EPS) of bacterial biofilms prevent antibacterial materials reaching the interior. 31,32 Liposomes can adhere to the bacterial membrane and deliver antibacterial materials to the bacteria. 33,34 Therefore, it is necessary to integrate PDA, MnO 2 , the photosensitizer and liposomes together for achieving chemo-photodynamic therapy.…”

Interfacial Affinity Determined Photocatalytic Activity: A Comparison between Defective and Bulk Polymeric Carbon Nitride

“…Which step is the rate-determining one for photocatalytic reactions depends on peculiarity of photocatalysts and substrates. For different photocatalytic applications of one photocatalyst, the difference in the photocatalytic processes only lies in the interfacial redox reactions for which to occur, the premise is certainly strong affinity between the photocatalyst and substrates because the photogenerated electrons and holes cannot exist in solutions and even the diffusion distance of generated reactive oxygen species (ROS) in solutions is quite short . The proposed affinity between photocatalysts and substrates here includes wettability for water splitting and adsorption for contaminant degradation, organic transformation, and gas reactions (e.g., nitrogen fixation, CO 2 reduction, and NO oxidation).…”

“…For different photocatalytic applications of one photocatalyst, the difference in the photocatalytic processes only lies in the interfacial redox reactions for which to occur, the premise is certainly strong affinity between the photocatalyst and substrates because the photogenerated electrons and holes cannot exist in solutions 5 and even the diffusion distance of generated reactive oxygen species (ROS) in solutions is quite short. 6 The proposed affinity between photocatalysts and substrates here includes wettability for water splitting and adsorption for contaminant degradation, organic transformation, and gas reactions (e.g., nitrogen fixation, CO 2 reduction, and NO oxidation). Generally, the photogenerated charge separation efficiency was considered to play the key role in the photocatalytic activity enhancement in water splitting and contaminant degradation, 7,8 suggesting that it was the rate-determining step.…”