TS41 is a trisulfide-derived ionizable lipid engineered for lipid nanoparticles (LNPs) to deliver mRNA therapeutics against multidrug-resistant bacterial pneumonia. Its optimized formulation, TS41S LNP, combines TS41 with helper lipids (e.g., DOPE, cholesterol) at a precise ratio, achieving a hydrodynamic diameter of ~105 nm, low polydispersity, and high mRNA encapsulation efficiency (~84%). This design enables efficient pulmonary delivery via intratracheal administration, with luminescence signals in lungs 4.8-fold higher than clinical benchmarks like SM-102 LNPs, ensuring targeted expression in epithelial cells, macrophages, and neutrophils. Crucially, TS41 LNPs exhibit potent anti-inflammatory properties by scavenging reactive oxygen species (ROS), reducing neutrophil infiltration and proinflammatory cytokines (e.g., IL-6, TNF-α) in infected lungs. In preclinical models, TS41S LNP encoding PB9 peptibody mRNA eradicated pathogens like Staphylococcus aureus and Pseudomonas aeruginosa, improved survival rates to 80%, and minimized tissue damage without systemic toxicity. Its ROS-scavenging capability synergizes with antibacterial effects, offering a promising, translatable platform for combating resistant infections while controlling inflammation. Future enhancements, such as codon optimization or inhalation delivery, could further broaden its therapeutic potential.
Cat.No
DC67657
Name
Lipid TS41
Chemical Properties
CAS
Formula
MW
Storage
2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
References
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