Stealth lipid nanoparticle compositions for cell targeting

A stealth lipid nanoparticle (LNP) comprising:

• (a) a therapeutic nucleic acid (TNA);
• (b) an ionizable lipid;
• (c) a sterol;
• (d) a first lipid-anchored polymer comprising a first hydrophilic polymer and a first lipid-linker, wherein the first lipid-linker comprises a first lipid comprising at least two hydrophobic tails, and wherein each hydrophobic tail comprises a carbon chain having 18 carbon atoms (C18);
• and
• (e) a second lipid-anchored polymer comprising a second hydrophilic polymer, a second lipid-linker, and a reactive moiety conjugated to a targeting moiety;
• wherein the second lipid-linker comprises a second lipid comprising at least two hydrophobic tails, wherein each hydrophobic tail comprises a carbon chain having 18 carbon atoms (C18),
• wherein the first lipid-anchored polymer and the second lipid-anchored polymer each independently comprise a polymer selected from the group consisting of polyethylene glycol (PEG), polyglycerol (PG), and combinations thereof, and
• wherein the first lipid-anchored polymer and the second lipid-anchored polymer are present at a combined molar percentage of about 2% to about 5%, and the second lipid-anchored polymer is present at a molar percentage of about 0.01% to about 2%.