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oai:figshare.com:article/34030497 2026-09-30T07:16:30Z category_4 category_12 category_13 category_14 category_873 category_39 category_46 category_734 category_62 category_64 category_69 portal_63 item_type_6 month_year_09_2026

Hybrid Exosome-Bilosome Oxygen Nanobubbles for Liver Fibrosis Attenuation: Antifibrotic Efficacy Investigation in Multilineage Spheroid Platform Anika Bushra (21023420) Eden Oelze (25142334) Thomas Locke (10092789) Dalton Jayne (25142337) Xiaoxue Han (8139150) Timothy M. Fan (675963) Joseph Irudayaraj (225666) Biochemistry Cell Biology Genetics Molecular Biology Chemical Sciences not elsewhere classified Ecology Immunology Biological Sciences not elsewhere classified Marine Biology Cancer Inorganic Chemistry term oral tolerability results confirmed suppression like vesicles utilized hypoxic hepatic microenvironment hepg2 cell lines hepatic spheroid model demonstrated excellent protection mediated fibrosis model fibrotic signaling (< encapsulating nanobubble (< reactive oxygen species oxygen loading capacity 50 nm size significant antifibrotic effect antifibrotic efficacy investigation addressing hypoxia associated bilosome oxygen nanobubbles >) associated genes induced hepatic damage elevated oxidative stress liver fibrosis attenuation bilosome oxygen hypoxia (< induced damage oxidative stress alongside oxygen 50 mg liver fibrosis antifibrotic properties antifibrotic cargo induced lipotoxicity localized hypoxia cellular hypoxia antifibrotic potential validating short shelf life scar tissue safety profile palmitic acid oleic acid often presents may contribute hybrid exosome hepatocellular carcinoma excessive buildup derived exosome delivering antioxidant Liver fibrosis refers to the excessive buildup of scar tissue in the liver, which can lead to cirrhosis and hepatocellular carcinoma. It often presents with a hypoxic hepatic microenvironment and elevated oxidative stress. In this work, we present a hybrid Exosome-Bilosome Oxygen-encapsulating Nanobubble (<i>EBON</i>) with antifibrotic properties that has the potential to protect the liver from localized hypoxia and oxidative stress-induced hepatic damage. Grapefruit-derived exosome-like vesicles utilized here may contribute to the therapeutic potential of the <i>EBON</i> formulation by delivering antioxidant, anti-inflammatory, and antifibrotic cargo, alongside oxygen. <i>EBON</i> has a sub-50 nm size with an oxygen loading capacity of about 50 mg/L and a shelf life of half a year. <i>EBON</i> has demonstrated excellent protection against cellular hypoxia, reactive oxygen species, and superoxide-induced damage in LX-2 and HepG2 cell lines. Additionally, <i>EBON</i> has shown a significant antifibrotic effect in palmitic acid and oleic acid-induced lipotoxicity and oxidative stress-mediated fibrosis model in LX-2/HepG2 multilineage hepatic spheroids. <i>RT-qPCR</i> results confirmed suppression of hypoxia (<i>HIF-1α</i>, <i>VEGF-A</i>), oxidative stress (<i>Nrf2</i>), and pro-fibrotic signaling (<i>α-SMA</i>, <i>TGF-β1</i>, and <i>COL1A1</i>) associated genes in the <i>in vitro</i> hepatic spheroid model. Additionally, the safety profile of <i>EBON</i> has been established in a 14-day murine oral gavage model, validating short-term oral tolerability. We propose that the hybrid Exosome-Bilosome Oxygen encapsulating Nanobubble reported here is a proof-of-concept platform with antifibrotic potential for addressing hypoxia associated with liver fibrosis. 2026-09-30T00:00:00Z Text Journal contribution 10.1021/acsnanomed.6c00127.s001 https://figshare.com/articles/journal_contribution/Hybrid_Exosome-Bilosome_Oxygen_Nanobubbles_for_Liver_Fibrosis_Attenuation_Antifibrotic_Efficacy_Investigation_in_Multilineage_Spheroid_Platform/34030497 CC BY-NC 4.0