2026-10-10T22:46:13Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33703090 2026-09-13T14:06:46Z category_1 category_4 category_7 category_12 category_13 category_14 category_16 category_19 category_272 category_873 category_931 category_64 portal_63 item_type_2 month_year_09_2026

Scavenger Receptor Class B Type 1 Mediated Transport Enables Delivery Across Capillarized Liver Sinusoids in Metabolic Dysfunction-Associated Steatohepatitis Ruyan Yuan (24857263) Jiamin Zhang (673881) Yamei Huang (6046262) Yiyang Meng (24857266) Siyan Liu (3471815) Wanqing Yang (11579356) Xinru Zhang (1598737) Mengyu Yang (11564897) Menglei Liang (24857269) Yipei Huang (11651614) Chang Liu (35901) Zhaoxia Cheng (11372814) Xiaotian Li (394967) Cong Wang (107450) Jundong Yao (21264833) Xiao Zhang (152326) Dongdong Zhang (644246) Ying Zhao (16546) Fenfen Li (4401631) Lei Wang (6656) Biophysics Biochemistry Medicine Cell Biology Genetics Molecular Biology Physiology Pharmacology Environmental Sciences not elsewhere classified Chemical Sciences not elsewhere classified Information Systems not elsewhere classified Cancer suppressed hsc activation modified lipid moiety lacks effective therapies hepatic stellate cells associated endothelial transport capillarized sinusoidal endothelium capillarized sinusoidal barrier responsive design increased associated fibrotic regions mimetic srb peptide sinusoidal exchange responsive linker fibrotic microenvironment restrict trans relative accessibility perisinusoidal space metabolic dysfunction lsec monolayer findings suggest fibrosis progresses collagen deposition become defenestrated Liver fibrosis in metabolic dysfunction associated steatohepatitis (MASH) lacks effective therapies, in part because therapeutic agents poorly penetrate the capillarized sinusoidal endothelium. As fibrosis progresses, liver sinusoidal endothelial cells (LSECs) become defenestrated and restrict trans-sinusoidal exchange, thereby limiting drug access to hepatic stellate cells (HSCs) within the perisinusoidal space. Here, we developed a lipoprotein mimetic liposomal nanocarrier, SV@SRB-Lip, to exploit scavenger receptor class B type 1 (SR-B1)-associated transendothelial transport across capillarized LSECs and enhance downstream delivery toward HSC-associated fibrotic regions. SV@SRB-Lip was engineered as a simvastatin loaded liposomal platform incorporating an ApoA-I-mimetic SRB peptide, an MMP-responsive linker, and a vitamin A modified lipid moiety. SV@SRB-Lip promoted transport across the LSEC monolayer in vitro, and this effect was reduced by SR-B1 silencing, supporting the involvement of SR-B1-associated endothelial transport. In MASH mice, SV@SRB-Lip enhanced hepatic delivery and distributed toward HSC associated fibrotic regions. The MMP-responsive design increased the relative accessibility of vitamin A within the fibrotic microenvironment, supporting downstream HSC associated uptake. As a result, SV@SRB-Lip increased hepatic simvastatin accumulation, suppressed HSC activation and collagen deposition, and improved MASH associated fibrosis. These findings suggest that SR-B1-associated endothelial transport can be harnessed to overcome the capillarized sinusoidal barrier and improve antifibrotic nanomedicine delivery in MASH. 2026-09-13T00:00:00Z Dataset Media 10.1021/acsnano.6c05500.s006 https://figshare.com/articles/media/Scavenger_Receptor_Class_B_Type_1_Mediated_Transport_Enables_Delivery_Across_Capillarized_Liver_Sinusoids_in_Metabolic_Dysfunction-Associated_Steatohepatitis/33703090 CC BY-NC 4.0