Multidrug-resistant, Gram-negative infection is a major global determinant of morbidity, mortality and cost of care. The advent of nanomedicine has enabled tailored engineering of macromolecular constructs, permitting increasingly selective targeting, alteration of volume of distribution and activity/toxicity. Macromolecules tend to passively and preferentially accumulate at sites of enhanced vascular permeability and are then retained. This enhanced permeability and retention (EPR) effect, whilst recognized as a major breakthrough in anti-tumoral targeting, has not yet been fully exploited in infection. Shared pathophysiological pathways in both cancer and infection are evident and a number of novel nanomedicines have shown promise in selective, passive, size-mediated targeting to infection. This review describes the similarities and parallels in pathophysiological pathways at molecular, cellular and circulatory levels between inflammation/infection and cancer therapy, where use of this principle has been established.

Acquisition of a mucoid phenotype byPseudomonassp. in the lungs of cystic fibrosis (CF) patients, with subsequent over-production of extracellular polymeric substance (EPS), plays an important role in mediating the persistence of multi-drug resistant (MDR) infections. The ability of a low molecular weight (Mn = 3200 g mol⁻¹) alginate oligomer (OligoG CF-5/20) to modify biofilm structure of mucoidPseudomonas aeruginosa(NH57388A) was studied in vitro using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) with Texas Red (TxRd®)-labelled OligoG and EPS histochemical staining. Structural changes in treated biofilms were quantified using COMSTAT image-analysis software of CLSM z-stack images, and nanoparticle diffusion. Interactions between the oligomers, Ca²⁺and DNA were studied using molecular dynamics (MD) simulations, Fourier transform infrared spectroscopy (FTIR) and isothermal titration calorimetry (ITC). Imaging demonstrated that OligoG treatment (≥0.5%) inhibited biofilm formation, revealing a significant reduction in both biomass and biofilm height (P < 0.05). TxRd®-labelled oligomers readily diffused into established (24 h) biofilms. OligoG treatment (≥2%) induced alterations in the EPS of established biofilms; significantly reducing the structural quantities of EPS polysaccharides, and extracellular (e)DNA (P < 0.05) with a corresponding increase in nanoparticle diffusion (P < 0.05) and antibiotic efficacy against established biofilms. ITC demonstrated an absence of rapid complex formation between DNA and OligoG and confirmed the interactions of OligoG with Ca²⁺evident in FTIR and MD modelling. The ability of OligoG to diffuse into biofilms, potentiate antibiotic activity, disrupt DNA-Ca²⁺-DNA bridges and biofilm EPS matrix highlights its potential for the treatment of biofilm-related infections.