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Development of an innovative extracellular vesicle mimetic delivery platform for efficient miRNA delivery to tumours

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dc.contributor.authorChen, R.
dc.contributor.authorBhavsar, C.
dc.contributor.authorLourie, R.
dc.contributor.authorLi, S.
dc.contributor.authorWu, S.Y.
dc.date.issued2025
dc.description.abstractExtracellular vesicles (EVs) display high degree of tissue tropism and therefore represent promising carriers for tissue-specific delivery of genes or drugs for the treatment of human diseases. However, current approaches for the loading of therapeutics into EVs have low entrapment efficiency and also do not adequately deplete endogenous EV content; thus, more effective approaches are needed. Here, we report an innovative EXtraCElluar vesicle surface Ligand-NanoParticles (EXCEL NPs), generated by transferring moieties of EVs onto the surface of synthetic nanoparticles. EXCEL NPs facilitate the efficient entrapment of therapeutics (89 % efficiency) and are completely devoid of pre-existing unwanted EV internal content. Importantly, we show that EXCEL NPs formulated using EVs derived from endothelial cells, astrocytes and macrophages retain the delivery characteristics of the original EVs. Using miRNA-146a as a model anti-cancer therapeutic, we further demonstrated successful delivery of miRNA-146a to IG10 orthotopic ovarian tumours in immune competent mice using EXCEL NPs formulated with macrophage-derived EVs. Our findings establish a new clinically translatable approach to leverage characteristics of endogenous EVs for therapeutic delivery. The versatility of the platform enables future application to different target cell types and therapeutic modalities.
dc.description.statementofresponsibilityRui Chen, Chintan Bhavsar, Rohan Lourie, Shuying Li, Sherry Y. Wu
dc.identifier.citationBiomaterials, 2025; 321:123282-1-123282-12
dc.identifier.doi10.1016/j.biomaterials.2025.123282
dc.identifier.issn0142-9612
dc.identifier.issn0142-9612
dc.identifier.orcidChen, R. [0000-0003-4671-4538]
dc.identifier.urihttps://hdl.handle.net/2440/146774
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/APP1162413
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/APP2020137
dc.rights© 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.source.urihttps://doi.org/10.1016/j.biomaterials.2025.123282
dc.subjectExtracellular vesicles; Biomimetic nanoparticles; Gene delivery; Cancer therapy
dc.titleDevelopment of an innovative extracellular vesicle mimetic delivery platform for efficient miRNA delivery to tumours
dc.typeJournal article
pubs.publication-statusPublished

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