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Table 4 Summary of peptides utilization as targeting moieties on the surface of nanosystems to combat bacterial sepsis

From: Applications of peptides in nanosystems for diagnosing and managing bacterial sepsis

Nanosystem

Peptide sequence

Biological target

Loaded drug

Key characterization

Key findings

Reference

PLGA nanoparticles

cyclo(1,12)PenITDGEATDSGC (cLABL) peptide

ICAM-1

NA

DLS

Cellular binding and uptake.

Size: 244 ± 15 nm; PDI: 0.215; ZP: -23.3 ± 1.0 mV.

Superior binding and internalization into interferon -γ-treated HUVECs cells.

[187]

PLGA nanoparticles

γ3 peptide (NNQKIVNLKEKVAQLEA)

ICAM-1

SFX

TAC

TEM

DLS

LC & EE%

In vitro drug release.

Cellular uptake.

In vitro and In vivo efficacy.

Shape: Spherical; size: 183.7 ± 9.4 nm; ZP: -40 mV; LC: (SFX: 15.47 ± 0.91, TAC: 20.22 ± 1.16); EE%: (SFX: 50.73± 4.09, TAC: 63.39 ± 3.52).

Sustained drug release.

2 to 3 times more uptake by TNF-α activated cells

Superior in vitro and in vivo antibacterial and anti-inflammatory efficacy.

[188]

PLGA nanoparticles

γ3 peptide (NNQKIVNLKEKVAQLEA)

ICAM-1

Ciprofloxacin

TEM

DLS

In vitro drug release.

Cellular uptake.

In vitro and In vivo efficacy.

Shape: core-shelled nanoparticles; size: 157 nm; ZP: -22 mV.

Sustained drug release.

Superior uptake by TNF-α activated cells.

Superior in vitro and in vivo antibacterial and anti-inflammatory efficacy.

[189]

Liposomes

RGD

Integrin

Curcumin

TEM

DLS

LC & EE%

Cellular Targeting Assay.

Antipyroptosis Assay.

In vitro ROS scavenging.

In vivo efficacy.

Shape: disc-like; size: 41.95 ± 19.85 nm; PDI: 0.228 ± 0.127; LC: 22.2 ± 1.4%; EE%: 99.9 ± 1.1%.

Superior uptake by LPS-stimulated RAW264.7 cells.

Significant in vitro reduction in intracellular ROS and inhibition of pyroptosis.

Remarkable inhibition of cytokines release (TNF-α and IL-6) and organ damage in mice.

[190]

HMPDA

Cys-LSA peptide (CLSALTPSPSWLKYKAL)

Dipeptidase 1

BAPTA-AM

NAD+

DLS

LC & EE%

Intracellular Energy Homeostasis restoration.

In vivo accumulation and antisepsis efficacy.

Size: 75.3 nm; ZP: -2.1 mV; LC: (NAD+: 23.8%, BAPTA-AM: 38.3%); EE%: (NAD+: 20.5%, BAPTA-AM: 57.9%).

Superior restoration of mitochondrial function, intracellular Ca++ hemostasis, and antioxidant activity.

Superior accumulation in liver, kidney, and lung of mice with LPS-induced sepsis.

Prevention of organ damage with improved survival rates in septic mice.

[191]

MSN

WLSEAGPVVTVRALRGTGSW

Primary cardiomyocytes

L-arginine

TEM

DLS

In vitro drug release.

In vitro cellular uptake.

In vivo biodistribution and efficacy.

Shape: spherical; size: 186.67 nm; ZP: -6.23 mV.

LIFU-responsive release: increased from 11.5% to 25.6% at pH 7.4.

Higher affinity and localization at cardiomyocytes compared to other cells.

Significantly higher distribution and accumulation in mice's hearts than in other organs.

Effective prevention of sepsis-induced cardiac injury in mice.

[192]

Zeolite imidazolate framework-8 nanoparticles

KCSAVPLC

Kidney cells

FGF21

TEM

DLS

In vitro drug release.

Cellular uptake.

In vitro cytoprotective effect.

In vivo biodistribution and efficacy.

Shape: polyhedral; size: 120.1 ± 5.4 nm; ZP: -17.4 ± 1.4 mV; pH-responsive drug release.

Significantly higher in vitro uptake by renal cellular.

Superior in vitro antioxidant, anti-inflammatory, and antiapoptotic efficacy on renal cells.

Preferable accumulation in kidneys and better recovery of renal function in LPS-induced septic mice.

[193]

GBPs

D-/L-Cys-Phe (CF) dipeptide

Bacterial cells

NA

TEM and SEM.

Photothermal properties assay.

Bacterial cell affinity assay.

In vitro and In vivo efficacy.

Shape: a spike shape (sea cucumber-like morphology); size: (Length: 200 ± 5.3 nm; width: 50 ± 2.8 nm).

Higher bacterial cell affinity with the D-CF coating gave higher adsorption than L-CF.

Significantly improved in vitro and in vivo efficacy.

[194]

  1. ICAM-1 Intercellular Adhesion Molecule-1, DLS Dynamic light scattering, PDI Polydispersity index, ZP Zeta potential, HUVECs Human umbilical cord vascular endothelial cells, SFX Sparfloxacin, TAC Tacrolimus, TEM Transmission electron microscopy, LC Loading capacity, EE% Encapsulation efficiency, TNF-α Tumor necrosis factor-α, ROS Reactive oxygen species, IL-6 Interleukin-6, HMPDA Hollow mesoporous polydopamine nanocarrier, BAPTA-AM BA-AM, O O′-bis(2-aminophenyl) ethylene glycol-N,N,N′,N′-tetra acetic acid, tetra acetoxymethyl ester, NAD+ Nicotinamide adenine dinucleotide, LPS Lipopolysaccharides, MSN Mesoporous silica nanoparticles, LIFU Low-intensity focused ultrasound, FGF21 fibroblast growth factor 21, GBPs Chiral gold nano-bipyramids, D-CF Dextro isomer of Cys-Phe dipeptide, L-CF Levo isomer of Cys-Phe dipeptide