POS4-0431
Click Chemistry-Mediated LNP Surface Modification for Targeted Extrahepatic Delivery
Topic
S4. Colloids, Interfaces, and Molecular Assemblies for Functional Soft Materials
When and Where
Sep 29, 2026
08:30 - 09:30
Room 301 (Grand Ballroom)
Session Chairs
Hae Jung SON
Boseok KANG
Presenter(s)
Seeun Kim (POSTECH)
Co-Author(s)
Abstract
Lipid nanoparticles (LNPs) represent a key delivery platform for nucleic acid therapeutics, and their successful clinical use depends on producing uniform particles as well as on effective delivery to targeted tissues other than the liver, where LNPs naturally accumulate. To enable uniform and scalable production, we developed a 3D-printed milli-fluidic mixing-extrusion device for LNP manufacturing. Then, we incorporated click-reactive lipids into LNPs and optimized their formulations to achieve stable physicochemical properties, including uniform particle size (~100 nm), low polydispersity (PDI < 0.2), and high encapsulation efficiency. Evaluation of the in vivo biodistribution of these click-functionalized LNPs revealed that DBCO-bearing LNPs exhibits the strongest hepatic evasion. Based on this result, we further examined how the biodistribution changed with DBCO content and found optimal liver avoidance at 0.5 mol% as contents above 0.9 mol% reduced colloidal stability. Building upon these liver-evading DBCO-LNPs, we plan to conjugate azide-bearing functional ligands through subsequent click reaction to actively target extrahepatic organs and tissues.
