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Atomic Insights into pH-Dependent and Water Permeation of mRNA-Lipid Nanoparticles.

Mol Pharm

January 2025

Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029, China.

The exposure of mRNA to water is likely to contribute to the instability of RNA vaccines upon storage under nonfrozen conditions. Using atomistic molecular dynamics (MD) simulations, we investigated the pH-dependent structural transition and water penetration behavior of mRNA-lipid nanoparticles (LNPs) with the compositions of Moderna and Pfizer vaccines against COVID-19 in an aqueous solution. It was revealed that the ionizable lipid (IL) membranes of LNPs were extremely sensitive to pH, and the increased acidity could cause a rapid membrane collapse and hydration swelling of LNP, confirming the high releasing efficiency of both LNP vaccines.

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The utilization of targeted nanoparticles as a selective drug delivery system is a powerful tool to increase the amount of active substance reaching the target site. This can increase therapeutic efficacy while reducing adverse drug effects. However, nanoparticles face several challenges: upon injection, the immediate adhesion of plasma proteins may mask targeting ligands, thereby diminishing the target cell selectivity.

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Intracellular trafficking of lipid nanoparticles is hindered by cholesterol.

Int J Pharm

January 2025

College of Pharmacy, DaLi University, No. 2 Hongsheng Road, Dali, Yunnan Province 671003, China; Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan, Dali University, Xueren Road, Dali, Yunnan Province 671003, China; Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan Province 671003, China. Electronic address:

The intracellular trafficking of lipid nanoparticles (LNPs) leading to endosomal escape is critical for delivery efficiency. How components of LNP affect its intracellular trafficking and delivery efficiency remains unknown. Here, we developed a highly sensitive LNP/nucleic acid tracking platform based on streptavidin-biotin-DNA complex and high throughput imaging.

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Development of a StIW111C-based bioresponsive pore-forming conjugate for permeabilizing the endosomal membrane.

Int J Biol Macromol

January 2025

Center for Protein Studies, Faculty of Biology, University of Havana (UH), 25(th) Street, corner to J Street. Square of Revolution, Havana 10400. Cuba; NanoCancer, Molecular Immunology Center (CIM), 216 Street, corner to 15 Street, Playa, Havana 11600, Cuba. Electronic address:

Gene expression manipulation is pivotal in therapeutic approaches for various diseases. Non-viral delivery systems present a safer alternative to viral vectors, with reduced immunogenicity and toxicity. However, their effectiveness in promoting endosomal escape, a crucial step in gene transfer, remains limited.

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Solid tumors (particularly the desmoplastic ones) usually harbor insurmountable mechanical barriers and formidable immunosuppressive tumor microenvironment (TME), which severely restricted nanomedicine-penetration and vastly crippled outcomes of numerous therapies. To overcome these barriers, a versatile nanoplatform orchestrated mechanotherapy with chemoimmunotherapy was developed here to simultaneously modulate tumor physical barriers and remodel TME for synergistically enhancing anticancer efficiency. Dexamethasone (DMS) and cis-aconityl-doxorubicin (CAD) were co-hitchhiked into phenylboronic acid functionalized polyethylenimine (PEI-PBA) carrier, and further in situ shielded by aldehyde-modified polyethylene glycol (PEG) to form CAD/DMS@PEG/PEI-PBA (CD@PB) nanoparticles (NPs).

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