Co-administration of lipid nanoparticles and cationic amphiphilic drugs to improve RNA delivery for cancer therapy

Jonas Steenbrugge – Postdoctoral researcher, Ghent University; Evelyne Meyer – Professor, Ghent University; Aliona Debisschop – PhD student, Ghent University; Kristel Demeyere – Lab responsible, Ghent University; Lars Koeken – PhD student, Ghent University; Ine Lentacker – Professor, Ghent University; Koen Raemdonck – Professor, Ghent University

Introduction:

Immune checkpoint blockade (ICB) has shown success across many cancer types, yet resistance is seen due to a cold, immunosuppressive tumor microenvironment (TME). It has been reported that antihistamines can boost ICB efficacy by reprogramming tumor-associated macrophages from an M2‑like pro-tumorigenic phenotype to an M1‑like anti-tumorigenic phenotype [1]. Many antihistamines are cationic amphiphilic drugs (CADs), small molecules with a hydrophilic and hydrophobic moiety, that can improve RNA delivery by promoting endosomal escape [2]. This project investigates the combination of RNA-loaded lipid nanoparticles (LNPs) and antihistamine CADs to achieve targeted delivery to the TME.