Original ArticleNanotheranostic approaches for management of bloodstream bacterial infections
Graphical Abstract
Section snippets
Existing methodologies for laboratory diagnosis and therapy of bacterial infections and their challenges
One of the main challenges of pathogen detection at early stages of infection is their low numbers in the clinical specimen. For example, in case of typhoid fever, number of Salmonella typhi is approximately 1 to 10 bacteria per milliliter of extracorporeal blood.21, 22 This number is comparable to that of circulating tumor cells (CTCs) in metastatic carcinoma, presenting the same, if not higher, degree of difficulty in their isolation and early identification.23, 24 As a result, a number of
Organic NPs
Organic NPs are carbon-based nanomaterials typically available in the size range from 10 nm to 1 μm.51 One of the most widely used types is polymer beads made out of polystyrene (PS) or polymethyl methacrylate (PMMA) commonly known as latex.52, 53 Latex microspheres are available with many different types of functional group chemistries (−COOH, −NH3, SO32− etc.) or surface coatings (dextran etc.) for use in a variety of diagnostic tests and bioassays. For e.g. streptavidin-coated beads are
Strategies for designing a novel bacterial nanotheranostic system
As discussed above, nanomaterial synthesis can be tailored to give particles of different shapes, sizes, types, morphology, texture (solid, porous, etc.), functionality and surface properties based on the nature of application.90 This ease of establishing tunability in material-functional relationships enables the facile use of NPs as theranostic agents when conceptualizing new platform strategies for dealing with infectious diseases. Before discussing these strategies, however, it is necessary
Conventional ligands
There are many different types of biomolecular ligands that have been traditionally used for specific binding to pathogen-specific components, namely antibodies, nucleic acids, carbohydrates, and small organic molecules (Figure 2). One or more of these biomolecules are attached to the NP surface and act as recognition elements for the components present on the bacterial surface.97, 107 Antibodies are typically the most expensive of all these molecules, requiring lengthy protocols for production
Limitations of drug-based theranostic ligands
In spite of the huge potential of antibiotics as theranostic ligands, not all drug molecules qualify the stringent selection criteria of being a good candidate for this application. Mainly membrane-active drugs such as PMB or daptomycin belonging to the peptide family may be used for this purpose as they act by binding to the surface of the bacteria and disrupting the cell membrane or altering its permeability leading to cell death. The same drug may be used for the treatment of that particular
Conclusions and outlook
With the increase in awareness and advancement in healthcare services across the world, the healthcare industry is also trying to match the best in terms of quality and service. There have been several advancements in diagnosis, therapeutic management and infrastructure all of which have improved the maintenance and recovery of critically-ill patients especially those in septic shock or multiorgan dysfunction syndrome. In spite of these, the mortality rate of patients who die of septic shock
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Conflict of interest: The authors report no conflicts of interest. Financial support in the form of junior research fellowship (JRF) to the first author was received from the Department of Science and Technology (DST), Government of India, New Delhi, India.