Advances in sepsis diagnosis and management: a paradigm shift towards nanotechnology

Abstract

Sepsis, a dysregulated immune response due to life-threatening organ dysfunction, caused by drug-resistant pathogens, is a major global health threat contributing to high disease burden. Clinical outcomes in sepsis depend on timely diagnosis and appropriate early therapeutic intervention. There is a growing interest in the evaluation of nanotechnology-based solutions for sepsis management due to the inherent and unique properties of these nano-sized systems. This review presents recent advancements in nanotechnology-based solutions for sepsis diagnosis and management. Development of nanosensors based on electrochemical, immunological or magnetic principals provide highly sensitive, selective and rapid detection of sepsis biomarkers such as procalcitonin and C-reactive protein and are reviewed extensively. Nanoparticle-based drug delivery of antibiotics in sepsis models have shown promising results in combating drug resistance. Surface functionalization with antimicrobial peptides further enhances efficacy by targeting pathogens or specific microenvironments. Various strategies in nanoformulations have demonstrated the ability to deliver antibiotics and anti-inflammatory agents, simultaneously, have been reviewed. The critical role of nanoformulations of other adjuvant therapies including antioxidant, antitoxins and extracorporeal blood purification in sepsis management are also highlighted. Nanodiagnostics and nanotherapeutics in sepsis have enormous potential and provide new perspectives in sepsis management, supported by promising future biomedical applications included in the review.

Keywords: Antimicrobial resistance; Nanodiagnostics; Nanotechnology; Nanotherapeutics; Sepsis.

Fig. 1

Pathophysiological changes in sepsis due to infection. Release of danger signal molecules (PAMP/ DAMP) activates the immune cells that mediate responses at the plasma protein level and the cellular level. Further downstream processes cause alterations in blood supply and oxygen consumption, leading to organ dysfunction

Fig. 2

Schematic presentation of general protocol and principle of different electrochemical sensors. a Potentiometric antibody immobilized ZnO nanotubes-based biosensor for the detection of CRP; the calibration curve of bare ZnO nanotubes for CRP-antigen (b) and antibody immobilized ZnO nanotubes for CRP (c) [64]. d Different steps involved in the preparation of the dual electrochemical immunosensor for multiplexed determination of IL-1b and TNF-α cytokines. Calibration plots for IL-1b (e) and TNF-α (f) obtained with the dual poly-HRP-Strept-Biotin-anti-IL-IL1b-anti-IL-Phe-DWCNTs/SPCE and poly-HRP-Strept-Biotin-anti-TNF-TNF-α-anti-TNF-Phe-DWCNTs/SPCE immunosensor [68]

Fig. 3

Schematic representation of the sandwich immunoassays: a NbI-GR-GS-GCE as a PCT capturing sensor and CdTe@SiO2/NbII to detect the PCT by ECL. The preparation of the CdTe@SiO2/NbII is also shown (dashed line box) [72]. b Fabrication of the electrochemical immunosensor for the detection of PCT [73] c Principle for Electrochemical Immunoassay Based on Poly[G]-Functionalized Silica NPs [74] d Assembly procedure of ALP-Ab2-GNPs/PSA bioconjugates [75]

Fig. 4

Effect on survival by different nano-antibiotic formulations. a Meropenem-loaded nanoparticles [91] b CARG-pSiNP-vancomycin [89] c CIP + TPCA-1-NPs-anti-ICAM-1 [94] d γ3-PLGA/S + T NPs [95]

Fig. 5

Fluorescence imaging studies using Optical Microscope eXperimental 3D-SIM images: Images of E. coli before (a) and after treatment with AF488-tagged SNAPP S16 (b–h). The E. coli cell membrane was stained with red and S16 with green in all images [100]

Fig. 6

HDL-like NP effect on suppressing TLR4 signalling. a General scheme for the synthesis of HDL-like NP. b Effect of different HDL-like NP and human HDL (hHDL) on inflammatory response when reporter cells treated with 1 ng/ml LPS from E. coli. c Inflammatory response of NP 1 or hHDL and LPS derived from the different bacterial species as indicated (****p ≤ 0.0001) [124]

Fig. 7

Formulation of macrophage membrane-coated NP (MΦ-NPs), a Schematic representation of the mechanism of endotoxin and proinflammatory cytokine neutralization. b Characterization by DSC, c Effect on survival based on in vivo studies [144]. d Biomimetic nanosponges and their mechanism of neutralizing pore-forming toxins e TEM visualization of nanosponges mixed with α-toxin, Survival rates of mice over 15 days after IV administration of blank or treatment agents 2 min either before (f) or after (g) the toxin injection [143]