Aptamer-LNP Conjugation Optimization for Targeted Drug Delivery: A Comparative Study

Khuloud T. Al-Jamal – Professor, King’s College London, UK and The University of Hong Kong; Mauro Giacca – Professor, King’s College London, UK and The University of Hong Kong; Osama Hassuneh – PhD student, The University of Hong Kong, Hong Kong; Alexandra R. Paul – Post-doc, King’s College London, UK and The University of Hong Kong; Adam A. Walters – Lecturer, King’s College London

Introduction:

Drug delivery using lipid nanoparticles (LNPs) is frequently constrained by non-specific cellular uptake. Aptamers provide high affinity and specificity for defined cell-surface receptors (1); however, their functional performance is highly dependent on the conjugation strategy used to attach them to nanoparticle surfaces. This study compares maleimide-thiol chemistry (2) with cholesterol-mediated anchoring (3) as two approaches for aptamer functionalization of LNPs.