Fluorous‐Tagged Peptide Nanoparticles Ameliorate Acute Lung Injury via Lysosomal Stabilization and Inflammation Inhibition in Pulmonary Macrophages

Abstract

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common respiratory critical syndrome that currently has no effective therapeutic interventions. Pulmonary macrophages play a principal role in the initiation and progression of the overwhelming inflammation in ALI/ARDS. Here, a type of fluorous‐tagged bioactive peptide nanoparticle termed CFF13F is developed, which can be efficiently internalized by macrophages and suppress the excessive expression of cytokines and the overproduction of reactive oxygen species (ROS) triggered by lipopolysaccharide (LPS). The cytoprotective effect of CFF13F may be attributed to the lysosomal‐stabilization property and regulation of the antioxidative system. Moreover, intratracheal pretreatment with CFF13F can effectively reduce local and systematic inflammation, and ameliorate pulmonary damage in an LPS‐induced ALI murine model. The therapeutic efficacy of CFF13F is affected by the administration routes, and the local intratracheal injection is found to be the optimal choice for ALI treatment, with preferred biodistribution profiles. The present study provides solid evidence of the potent immunomodulatory bioactivity of the fluorous‐tagged peptide nanoparticles CFF13F in vitro and in vivo, and sheds light on the development of novel efficient nanodrugs for ALI/ARDS.

Fluorous Tagged Peptides for Intracellular Delivery and Biomedical Imaging

“…CFF was conjugated with Tag 1 via the disulfide linkage and the conjugate was further assembled to form peptide nanoparticles ( Figure 2 ). [ 42 ] The nanoparticles were efficiently delivered into bone marrow‐derived macrophages, and inhibited lipopolysaccharide (LPS)‐induced inflammation and reactive oxygen species (ROS) in the treated cells. Transcriptomic results showed that the nanoparticle treatment influenced multiple signal pathways related to inflammation including the TLR signaling pathway, and also inhibited the expression of genes involved in NF‐ κ B and MAPK pathways.…”

“…CFF was conjugated with Tag 1 via the disulfide linkage and the conjugate was further assembled to form peptide nanoparticles (Figure 2). [42] The nanoparticles were efficiently delivered into bone marrow-derived macrophages, and inhibited Fluorous tagged CFF peptide for the treatment of LPS-induced acute lung injury. Reproduced with permission.…”

“…Reproduced with permission. [42] Copyright 2022, Wiley-VCH. lipopolysaccharide (LPS)-induced inflammation and reactive oxygen species (ROS) in the treated cells.…”

“…Figure 2.Fluorous tagged CFF peptide for the treatment of LPS-induced acute lung injury. Reproduced with permission [42]. Copyright 2022, Wiley-VCH.…”

Self‐Assembled Virus‐Like Particle Vaccines via Fluorophilic Interactions Enable Infection Mimicry and Immune Protection

“…[33,34] Notably, the high affinity of F─F interactions enables the synthesis of fluoroustagged peptides, which could self-assemble into nanoparticles for efficient intracellular peptide delivery. [35,36] Overall, the selfassembly behavior of fluorocarbon chains shows great potential for nanostructure preparation and drug delivery applications.…”