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Post-Assembly Functionalization of Maleimide-Derivatized Lipid Nanoparticles with Peptide and Antibody Ligands via Thiol-Maleimide Conjugation Chemistry
Introduction
Lipid nanoparticles (LNPs) are versatile carriers for nucleic acid delivery, yet their natural tropism toward the liver limits extra-hepatic applications. To overcome this limitation, surface modification with active targeting ligands has emerged as an effective strategy.
This technical note describes a unified approach for post-assembly functionalization of maleimide-derivatized LNPs using thiol-maleimide chemistry to attach two ligands with different molecular sizes:
- CREKA peptide (~0.7 kDa), a tumor-homing pentapeptide that binds fibrin-fibronectin complexes.
- Anti-CD3 monoclonal antibody (~150 kDa), an immunoglobulin targeting the CD3 receptor on T-cells.
By comparing both conjugation strategies, this study demonstrates the robustness and adaptability of the thiol-maleimide platform across ligands with vastly different molecular weights and structural complexities.
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