Yu Xu,Wen Jiang,Xin-Chuang Wang,Feng-Xian Luo,Jiang-Ning Hu
As a global public health issue, the treatment of acute liver injury (ALI) is facing serious challenges due to the lack of specific drugs. Selenium nanoparticles (Se NPs), due to their robust antioxidant attributes, have shown considerable potential in ALI prevention. However, the application of Se NPs is impeded by their instability, propensity to aggregate, and tendencies towards precipitation. In this study, we modified the surface of Se NPs with phlorotannin (PT) to synthesize PT-Se NPs. Our initial results suggested that PT-Se NPs, having a reduced particle size of 107.10 ± 4.04 nm, exhibited superior stability, enhanced cellular absorption, and sustained liver accumulation in comparison to Se NPs. In concordance with our expectations, PT-Se NPs demonstrated enhanced therapeutic performance in mitigating CCl 4 -induced ALI, as demonstrated by the preservation of liver functionality, decrease in oxidative stress markers, reduction of inflammatory factor levels, and improvement in histological damage. This research contributes a promising strategy for effectively improving the stability of Se NPs and preventing ALI, broadening the horizon for effective liver protection and potential clinical translation.
Lipid nanoparticles for mRNA delivery and gene editing have the potential to transform the current therapeutic landscape. Nonetheless, a major bottleneck using this technology is the difficulty in achieving cell- and tissue-specific delivery and avoiding liver accumulation. Here we report the rational design of peptide ionizable lipids to assemble lipid nanoparticles with organ-selective mRNA delivery. Structure–activity and structure–selectivity relationship analyses enable us to obtain a general and predictable strategy for peptide ionizable lipid design. By incorporating artificial ionizable and natural amino acids and/or functional molecules into peptide ionizable lipids, we create lipid nanoparticles with tissue-specific targeting, including the lungs, liver, spleen, thymus and bone. In particular, lipid nanoparticles containing peptide lipids targeting the liver show comparable efficacy and safety compared with FDA-approved formulations. Furthermore, lipid nanoparticles with peptide lipids achieve the efficient co-delivery of PEmax mRNA and engineered prime editing guide RNA for prime editing of the liver and lungs. Overall, our platform offers a predictable methodology for the rational design of tissue-targeting lipid nanoparticles that might aid the development of improved mRNA-based gene editing therapeutics.
危险品化学品经营许可证（带存储）