Illuminating endosomal escape of polymorphic lipid nanoparticles that boost mRNA delivery
文献信息
Marco Herrera, Jeonghwan Kim, Yulia Eygeris, Antony Jozic
Lipid-based nanoparticles (LNPs) for the delivery of mRNA have jumped to the forefront of non-viral gene delivery. Despite this exciting development, poor endosomal escape after LNP cell entry remains an unsolved, rate-limiting bottleneck. Here we report the use of a galectin 8-GFP (Gal8-GFP) cell reporter system to visualize the endosomal escape capabilities of LNP-encapsulated mRNA. LNPs substituted with phytosterols in place of cholesterol exhibited various levels of Gal8 recruitment in the Gal8-GFP reporter system. In live-cell imaging, LNPs containing β-sitosterol (LNP-Sito) showed a 10-fold increase in detectable endosomal perturbation events when compared to the standard cholesterol LNPs (LNP-Chol), suggesting the superior capability of LNP-Sito to escape from endosomal entrapment. Trafficking studies of these LNPs showed strong localization with late endosomes. This highly sensitive and robust Gal8-GFP reporter system can be a valuable tool to elucidate intricacies of LNP trafficking and ephemeral endosomal escape events, enabling advancements in gene delivery.
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来源期刊
Biomaterials Science
Biomaterials Science is an international high impact journal exploring the science of biomaterials and their translation towards clinical use. Its scope encompasses new concepts in biomaterials design, studies into the interaction of biomaterials with the body, and the use of materials to answer fundamental biological questions. Papers do not necessarily need to report a new biomaterial but should provide novel insight into the biological applications of the biomaterial. Articles that primarily focus on demonstrating novel materials chemistry and bring a molecular picture to bear on a given material’s suitability as a biomaterial are more suited to our companion journal, Journal of Materials Chemistry B. Biomaterials Science publishes primary research and review-type articles in the following areas: molecular design of biomaterials, including translation of emerging chemistries to biomaterials science of cells and materials at the nanoscale and microscale materials as model systems for stem cell and human biology materials for tissue engineering and regenerative medicine (Nano)materials and (nano)systems for therapeutic delivery interactions at the biointerface biologically inspired and biomimetic materials, including bio-inspired self-assembly systems and cell-inspired synthetic tools next-generation biomaterials tools and methods
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