Background Acute lung injury (ALI) is a life-threatening clinical syndrome without effective treatment. Targeting delivery of glucocorticoid to lung shows potential efficacy for ALI based on their anti-inflammatory and anti-fibrotic properties, breaking through their clinical application limitation due to systemic side effects. This work was aimed to establish lung-targeted dexamethasone (DEX) loaded nanostructured lipid carriers (NLCs) with opposite surface charge and investigate their therapeutic effects on lipopolysaccharide (LPS)-induced ALI mice.Results The diameter of anionic anti-intercellular adhesion molecule 1 (anti-ICAM-1) antibody-conjugated DEX-loaded NLCs (ICAM/DEX/NLCs) and the cationic ones with octadecylamine (ODA) modification (ICAM/DEX/ODA-NLCs) was about 249.9 and 235.9 nm. The zeta potential of ICAM/DEX/NLCs and ICAM/DEX/ODA-NLCs was about − 30.3 and 37.4 mV, respectively. Relative to the non-targeted control and ICAM/DEX/ODA-NLCs, ICAM/DEX/NLCs exhibited higher in vitro cellular uptake in LPS-activated human vascular endothelial cell line EAhy926 after CAM-mediated endocytosis, and stronger in vivo pulmonary distribution in the ALI model mice. In vivo i.v. administration of ICAM/DEX/NLCs significantly attenuated pulmonary inflammatory cells infiltration, and the production of pro-inflammatory cytokine TNF-α and IL-6 in ALI mice. H&E stain also revealed positive histological improvements by ICAM/DEX/NLCs.Conclusion sICAM/DEX/NLCs may represent a potential pulmonary endothelium targeted device, which facilitate translation of DEX into clinical ALI treatment.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and causes high ratios of morbidity and mortality worldwide. Although many potential therapeutic targets have been reported, the therapeutic effect needs to be further improved. Herein, we report a strategy to specifically target inflammation site via anti-ICAM-1 antibody bonded antibacterial peptides polymeric nanoparticle. Antibacterial peptide (KR-12) grafted amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 block copolymer and PCL- b -P(OEGMA- co -AMA)- g -biotin block copolymer were synthesized by ring-opening polymerization and click chemistry. Then, antibacterial peptides polymeric nanoparticles (AMPNP) were prepared by co-assembly of amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 and PCL- b -P(OEGMA- co -AMA)- g -biotin in aqueous solution. Intercellular adhesion molecule-1 (ICAM-1) is highly expressed on the surface of inflammatory endothelial cells, and the anti-ICAM-1 antibody can specifically bind to it. To obtain the anti-ICAM-1-AMPNP nanoparticles, biotinylated anti-ICAM-1 antibodies were bonded on the surface of AMPNP nanoparticles through the biotin-avidin system. The anti-ICAM-1-AMPNP nanoparticles had low systemic toxicity and exhibited ideal antibacterial property against drug-resistant bacteria, Gram-negative bacteria and Gram-positive bacteria. The anti-ICAM-1-AMPNP nanoparticles exhibited favorable targeting capabilities to inflammation endothelial cells in vitro and significantly reduced the inflammatory response of CLP mice in vivo . The present investigation might provide a specific strategy for targeting combating sepsis with anti-ICAM-1-AMPNP nanoparticles.
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