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Biofilm interfacial acidity evaluation by pH-Responsive luminescent nanoparticle films.

ABSTRACT: Biofilms are dense bacterial colonies that may adhere to the surfaces of medical devices and are major contributors to infections. These colonies are characterized by a self-produced matrix of extracellular polymeric substances (EPS). Bacterial biofilms are difficult to treat with the commonly used antibiotics partially because of their poor diffusion through the EPS and therefore require new targeted strategies to effectively fight them. Biofilms may produce an acidic microenvironment which can be exploited to design such targeted treatment strategies. However, there is currently a lack of high-throughput ways to determine the acidity of biofilms at their interface with the medical device. Here, a novel all-inorganic pH responsive system is developed from luminescent carbonated hydroxyapatite nanoparticles doped with Eu³⁺ ions which can determine the biofilm acidity fluorometrically due to carbonate removal in acidic environments that directly affects the nanoparticle luminescence. The pH responsive nanoparticles are in-situ deposited during their production onto substrates on which a variety of clinically-relevant biofilms are grown. The acidity of their interfacial (micro)environment depends on the bacterial species and strain even when differences in biofilm biomass are considered.

SUBMITTER: Merkl P

PROVIDER: S-EPMC7116521 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Biofilm interfacial acidity evaluation by pH-Responsive luminescent nanoparticle films.

Merkl Padryk P Aschtgen Marie-Stephanie MS Henriques-Normark Birgitta B Sotiriou Georgios A GA

Biosensors & bioelectronics 20201022

Biofilms are dense bacterial colonies that may adhere to the surfaces of medical devices and are major contributors to infections. These colonies are characterized by a self-produced matrix of extracellular polymeric substances (EPS). Bacterial biofilms are difficult to treat with the commonly used antibiotics partially because of their poor diffusion through the EPS and therefore require new targeted strategies to effectively fight them. Biofilms may produce an acidic microenvironment which can ...[more]

PMID: 33120233

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Project description:Protein subunit vaccines offer important potential advantages over live vaccine vectors but generally elicit weaker and shorter-lived cellular immune responses. Here we investigate the use of pH-responsive, endosomolytic polymer nanoparticles that were originally developed for RNA delivery as vaccine delivery vehicles for enhancing cellular and humoral immune responses. Micellar nanoparticles were assembled from amphiphilic diblock copolymers composed of an ampholytic core-forming block and a redesigned polycationic corona block doped with thiol-reactive pyridyl disulfide groups to enable dual-delivery of antigens and immunostimulatory CpG oligodeoxynucleotide (CpG ODN) adjuvants. Polymers assembled into 23 nm particles with simultaneous packaging of CpG ODN and a thiolated protein antigen, ovalbumin (ova). Conjugation of ova to nanoparticles significantly enhanced antigen cross-presentation in vitro relative to free ova or an unconjugated, physical mixture of the parent compounds. Subcutaneous vaccination of mice with ova-nanoparticle conjugates elicited a significantly higher CD8(+) T cell response (0.5% IFN-γ(+) of CD8(+)) compared to mice vaccinated with free ova or a physical mixture of the two components. Significantly, immunization with ova-nanoparticle conjugates electrostatically complexed with CpG ODN (dual-delivery) enhanced CD8(+) T cell responses (3.4% IFN-γ(+) of CD8(+)) 7-, 18-, and 8-fold relative to immunization with conjugates, ova administered with free CpG, or a formulation containing free ova and CpG complexed to micelles, respectively. Similarly, dual-delivery carriers significantly increased CD4(+)IFN-γ(+) (Th1) responses and elicited a balanced IgG1/IgG2c antibody response. Intradermal administration further augmented cellular immune responses, with dual-delivery carriers inducing ∼7% antigen-specific CD8(+) T cells. This work demonstrates the ability of pH-responsive, endosomolytic nanoparticles to actively promote antigen cross-presentation and augment cellular and humoral immune responses via dual-delivery of protein antigens and CpG ODN. Hence, pH-responsive polymeric nanoparticles offer promise as a delivery platform for protein subunit vaccines.

Dataset Information

Biofilm interfacial acidity evaluation by pH-Responsive luminescent nanoparticle films.

Publications

Biofilm interfacial acidity evaluation by pH-Responsive luminescent nanoparticle films.

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