Ionizable lipid nanoparticles have demonstrated remarkable success as mRNA vaccine carriers and represent one of the most promising gene drug delivery vehicles. However, polyethylene glycol (PEG), one of the major components, can cause immunogenic reactions, anaphylaxis and increased blood clearance, leading to toxic side effects and reduced efficacy. In this study, we utilize polysorbate 80 (PS80) as a PEG alternative in formulating eGFP mRNA-loaded ionizable lipid nanoparticles (PS80-iLNPs), aiming to enhance stealth properties, uptake efficiency, and biosafety. Our findings revealed that PS80-iLNPs enhanced the stealthiness and resistance to serum interference. Compared to PEG-containing ionizable lipid nanoparticles (PEG-iLNPs), PS80-iLNPs showed a 1.14-fold increase in stealthiness. Moreover, at a total lipid concentration of 50 μg mL, PS80-iLNPs exhibited 1.12 times higher cell viability compared to PEG-iLNPs. Notably, under serum interference, PEG-iLNPs showed a 44.97% uptake reduction, whereas PS80-iLNPs exhibited a modest 30.55% decrease, underscoring its superior serum resistance. This work demonstrated that PS80 could serve as a suitable substitute for PEG, thus signifying an excellent basis for the development of PEG-free ionizable lipid nanoparticles.
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http://dx.doi.org/10.1039/d4bm00523f | DOI Listing |
Adv Sci (Weinh)
January 2025
Department of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
Most gene therapies exert their actions via manipulation of hepatocytes (parenchymal cells) and the reasons behind the suboptimal performance of synthetic mRNA in non-parenchymal cells (NPC) such as Kupffer cells (KC), and liver macrophages, remain unclear. Here, the spatio-temporal distribution of mRNA encoding enhanced green fluorescent protein (Egfp), siRNA, or both co-encapsulated into lipid nanoparticles (LNP) in the liver in vivo using real-time intravital imaging is investigated. Although both KC and hepatocytes demonstrate comparable high and rapid uptake of mRNA-LNP and siRNA-LNP in vivo, the translation of Egfp mRNA occurs exclusively in hepatocytes during intravital imaging.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Suzhou CureMed Biopharma Technology Co., Ltd., Suzhou 215125, China.
The emergence of mRNA vaccines offers great promise and a potent platform in combating various diseases, notably COVID-19. Nevertheless, challenges such as inherent instability and potential side effects of current delivery systems underscore the critical need for the advancement of stable, safe, and efficacious mRNA vaccines. In this study, a robust mRNA vaccine (cmRNA-1130) eliciting potent immune activation has been developed from a biodegradable lipid with eight ester bonds in the branched tail (AX4) and synthetic circular mRNA (cmRNA) encoding the trimeric Delta receptor binding domain of the SARS-CoV-2 spike protein.
View Article and Find Full Text PDFArch Toxicol
January 2025
Department of Biochemistry and Microbiology, University of Chemistry and Technology, Technická 3, 16000, Prague, Czech Republic.
Chlorinated paraffins (CPs) are environmental pollutants extensively used in industries. While the use of short-chain chlorinated paraffins (SCCPs) has been restricted since 2017, the use of medium-chain chlorinated paraffins (MCCPs) has risen as their replacement. Due to lipophilic character, it can be expected that CPs enter the cells; however, the in vitro accumulation potential of CPs remains poorly understood.
View Article and Find Full Text PDFJ Adv Res
January 2025
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao 999078, China; Guangdong-Hong Kong-Macau Join Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research, University of Macau, Avenida da Universidade, Taipa, Macao 999078, China; Department of Pharmaceutical Sciences and Technology, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macao 999078, China. Electronic address:
Introduction: Non-alcoholic fatty liver disease (NAFLD) acts as the primary contributor to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and potentially hepatocellular carcinoma. The flowers of Chrysanthemum indicum, a traditional edible medicinal herb, have been widely used in China for more than 2000 years. However, the function of C.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Weill Cornell Medicine, New York, NY, USA
Background: Alzheimer's disease (AD) is associated with impaired lipid metabolism in the brain. To identify the specific regions where pathological change to cell functionality occurs, a spatial investigation of regional lipid dysregulation is needed.
Method: We measured untargeted spatial lipidomics using Desorption Electrospray Ionization (DESI) mass spectrometry in the brains of mice from two genotypes, wild type (WT) and APPsw, an AD mouse model overexpression amyloid precursor protein (APP).
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