Ligand-free hepatocyte-targeting of nanomedicines by selective stealth coating of liver reticuloendothelial system scavenger cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K18062
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine
• Principal Investigator: Dirisala Anjaneyulu 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 主任研究員 (70794353)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Liver blockade / Sinusoidal endothelium / Kupffer cells / Nanomedicine retargeting

Outline of Final Research Achievements

Site-specific delivery of nucleic acid therapeutics to liver parenchymal cells (hepatocytes) is a potential strategy for the treatment of many liver diseases. However, the biggest issue in hepatocyte-selective delivery of systemically administered nucleic acid therapeutics is nonspecific elimination by liver scavenger reticuloendothelial system (RES) [sinusoidal endothelial cells (SECs) and Kupffer cells (KCs)], causing a substantial decrease in delivery efficiency. In this study, we addressed this issue by selective masking of scavenger receptors of RES with PEG coating using a oligocation conjugated two-armed poly(ethylene glycol) to suppress the recognition and elimination of nucleic acid therapeutics by liver RES and thereby maximizing the delivery to hepatocytes.

Free Research Field

Biomedical engineering

Academic Significance and Societal Importance of the Research Achievements

Scientific significance: We developed in situ stealth coating technology for transient blockade of liver scavenger cells, and promoted nucleic acid therapeutic transfection.
Social significance: Our technology can increase the therapeutic potential of nanomedicines with lower doses without ligands.