Figure 1.

Schematic presentation showing the gene delivery by dual modified LNPs.

Notes: The nanoparticle is modified with angiopep for receptor-mediated uptake in LRP-1 expressing cells (left pathway) and a MMP-cleavable lipopeptide for activation in tumor tissue microenvironment (right pathway). Intra- or extracellular cleavage of the lipopeptide dePEGylates the LNP and reverses the surface charge from negative to positive leading to increased uptake and endosomal escape.

Abbreviations: LNPs, lipid nanoparticles; LRP-1, low-density lipoprotein receptor-related protein-1; PEG, poly(ethylene glycol).