Original Article
Nanotheranostic approaches for management of bloodstream bacterial infections

https://doi.org/10.1016/j.nano.2016.09.005Get rights and content

Highlights

  • It is one of the few comprehensive review papers on bacterial nanotheranostics covering all aspects of bloodstream bacterial infections, different classes of nanomaterials and bioreceptors, new-age drug ligands, present challenges in the field and future perspectives on applications of nanotheranostics with respect to infectious disease management.

  • In this paper we suggest two broad but specific strategies for designing an effective bacterial nanotheranostic system giving examples in the form of case studies.

Abstract

Bloodstream bacterial infections are a serious threat to global public health and economy. The recent figures released by National Center for Health Statistics indicate that more than a million Americans get affected by it each year and the sepsis mortality alone is about 28%-50% Hall et al. (2011).1 Robust and affordable point-of-care medical technologies are, therefore, urgently needed for rapid decision-making to initiate appropriate line of treatment. Current techniques based on blood culture and serology do not have quick turnaround times or adequate sensitivities for early intervention. Moreover, antimicrobial resistance poses a great challenge in the fight towards effective bacterial infection management. Nanotheranostics is emerging as a novel strategy combining solutions for rapid diagnosis and treatment in a more personalized way. This review highlights the recent advances made in theranosis of bloodstream bacterial infections using different classes of nanomaterials and bioreceptors, and discusses present challenges and future way forward.

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.

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