Ligand‐Tethered Extracellular Vesicles Mediated RNA Therapy for Liver Fibrosis DOI
Yue Liu, Shang Chen, Haoyan Huang

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 9, 2024

Liver fibrosis poses a significant global health burden, in which hepatic stellate cells (HSCs) play crucial role. Targeted nanomedicine delivery systems directed at HSCs have shown immense potential the treatment of liver fibrosis. Herein, bioinspired material, engineered therapeutic miR-181a-5p (a miRNA known to inhibit fibrotic signaling pathways) and targeted moiety hyaluronic acid (HA) co-functionalized extracellular vesicles (EVs) are developed. HA is incorporated onto surface EVs using DSPE-PEG as linker, allowing preferential binding CD44 receptors, overexpressed on activated HSCs. Our results confirmed enhanced cellular uptake improved payload delivery, evidenced by increased intracellular abundance livers. HA-equipped loaded with (DPH-EVs@miR) significantly reduce HSC activation matrix (ECM) deposition inhibiting TGF-β/Smad pathway, thus alleviating progression Additionally, DPH-EVs@miR improves function, ameliorates inflammatory infiltration, mitigates hepatocyte apoptosis, demonstrating superior protective effects. Collectively, this study reports prospective nanovesicle platform targeting motifs for The biomarker-guided EV-engineering technology utilized provides promising tool precision medicine.

Language: Английский

Why Do Lipid Nanoparticles Target the Liver? Understanding of Biodistribution and Liver-Specific Tropism DOI Creative Commons
Mahboubeh Hosseini-Kharat, Kristen E. Bremmell, Clive A. Prestidge

et al.

Molecular Therapy — Methods & Clinical Development, Journal Year: 2025, Volume and Issue: 33(1), P. 101436 - 101436

Published: Feb. 16, 2025

Lipid nanoparticles (LNPs) are now highly effective transporters of nucleic acids to the liver. This liver-specificity is largely due their association with certain serum proteins, most notably apolipoprotein E (ApoE), which directs them liver cells by binding low-density lipoprotein (LDL) receptors on hepatocytes. The liver's distinct anatomy, its various specialized cell types, also influences how LNPs taken up from circulation, cleared, and they in delivering treatments. In this review, we consider factors that facilitate LNP's targeting explore latest advances liver-targeted LNP technologies. Understanding targeted can help for design optimization nanoparticle-based therapies. Comprehension cellular interaction biodistribution not only leads better treatments diseases but delivers insight directing other tissues, potentially broadening range therapeutic applications.

Language: Английский

Citations

1
Ligand‐Tethered Extracellular Vesicles Mediated RNA Therapy for Liver Fibrosis DOI
Yue Liu, Shang Chen, Haoyan Huang

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 9, 2024

Liver fibrosis poses a significant global health burden, in which hepatic stellate cells (HSCs) play crucial role. Targeted nanomedicine delivery systems directed at HSCs have shown immense potential the treatment of liver fibrosis. Herein, bioinspired material, engineered therapeutic miR-181a-5p (a miRNA known to inhibit fibrotic signaling pathways) and targeted moiety hyaluronic acid (HA) co-functionalized extracellular vesicles (EVs) are developed. HA is incorporated onto surface EVs using DSPE-PEG as linker, allowing preferential binding CD44 receptors, overexpressed on activated HSCs. Our results confirmed enhanced cellular uptake improved payload delivery, evidenced by increased intracellular abundance livers. HA-equipped loaded with (DPH-EVs@miR) significantly reduce HSC activation matrix (ECM) deposition inhibiting TGF-β/Smad pathway, thus alleviating progression Additionally, DPH-EVs@miR improves function, ameliorates inflammatory infiltration, mitigates hepatocyte apoptosis, demonstrating superior protective effects. Collectively, this study reports prospective nanovesicle platform targeting motifs for The biomarker-guided EV-engineering technology utilized provides promising tool precision medicine.

Language: Английский

Citations

3