Conventional wound dressing materials containing free antibiotics for bacterial wound infections are presented with several limitations, that is, lack of controlled and triggered release capabilities, and may often not be adequate to address the complex bacteria microenvironment of such infections. Additionally, the improper usage of antibiotics may also result in the emergence of drug resistant strains. While delivery systems (i.e., nanoparticles) that encapsulate antibiotics may potentially overcome some of these limitations, their therapeutic outcomes are still less than desirable. For example, premature drug release or unintended drug activation may occur, which would greatly reduce treatment efficacy. To address this, responsive nanoparticle-based antimicrobial therapies could be a promising strategy. Such nanoparticles can be functionalized to react to a single stimulus or multi stimulus within the bacteria microenvironment and subsequently elicit a therapeutic response. Such “intelligent” nanoparticles can be designed to respond to the microenvironment, that is, an acidic pH, the presence of specific enzymes, bacterial toxins, etc. or to an external stimulus, for example, light, thermal, etc. These responsive nanoparticles can be further incorporated into wound dressings to better promote wound healing. This review summarizes and highlights the recent progress on such intelligent nanoparticle-based dressings as potential wound dressings for bacteria-infected wounds, along with the current challenges and prospects for these technologies to be successfully translated into the clinic.

Klebsiella pneumoniae is a foremost gram-negative pathogen that can induce life-threatening nosocomial pulmonary infections. Although it can be phagocytosed successfully by lung resident macrophages, this pathogen remains viable within vacuolar compartments, resulting in chronic infection and limiting therapeutic treatment with antibiotics. In this study, we aimed to generate and evaluate a cell-penetrant antibiotic poly(lactide-co-glycolide) (PLGA)-based formulation that could successfully treat intracellular K. pneumoniae infection. Screening of formulation conditions allowed the generation of high drug loaded nanoparticles through a water-in-oil-in-water approach. We demonstrated the therapeutic usefulness of these gentamicin-loaded nanoparticles (GNPs), showing their ability to improve survival and provide extended prophylactic protection towards K. pneumoniae using a Galleria mellonella infection model. We subsequently showed that the GNPs could be phagocytosed by K. pneumoniae infected macrophages, and significantly reduce the viability of the intracellular bacteria without further stimulation of pro-inflammatory or pro-apoptotic effects on the macrophages. Taken together, these results clearly show the potential to use antibiotic loaded NPs to treat intracellular K. pneumoniae infection, reducing bacterial viability without concomitant stimulation of inflammatory or pyroptotic pathways in the treated cells.

Lipid-coated hybrid nanoparticles are next-generation core–shell structured nanodelivery systems, which improve the loading capabilities of therapeutics and can improve therapeutic delivery, especially for targeting biofilm-based and intracellular bacterial infections.