Tuning lipid nanoparticle pKa to exploit the vitronectin corona for tumor-selective mRNA delivery to the lung

Lipid nanoparticles (LNPs) made mRNA medicines a clinical reality, but a stubborn problem has limited their reach in oncology: after intravenous injection, conventional LNPs accumulate overwhelmingly in the liver.1 Redirecting them to extrahepatic tumors has typically required chemically conjugating targeting ligands to the particle surface, an approach that adds manufacturing complexity and regulatory burden.2,3,4 In our study, recently published in the Journal of Controlled Release, we asked whether a single, formulation-level change to commercially available components could instead teach an LNP to deliver mRNA not merely to a specific organ, but preferentially to a tumor growing within that organ (Figure 1).