Lipid nanoparticle for targeted delivery of therapeutic payloads

A composition comprising a pharmaceutical agent assembled with a lipid composition comprising an ionizable lipid represented by Formula (III):

• or a pharmaceutically acceptable salt thereof;
• wherein:
• the Head is selected from the group consisting of
• wherein each Ra is independently selected from the group consisting of H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, 3- to 20-membered heterocycloalkyl, 1- to 20-membered heteroalkyl, C3-C7 carbocycle, and 3- to 7-membered heterocycle;
• each RLipid is independently selected from the group consisting of:
• Rk1 and Rk3 are each independently C1-C10 alkyl;
• each Rk2 is independently selected from the group consisting of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, 1- to 20-membered heteroalkyl, 3- to 20-membered heterocycloalkyl, aryl, and heteroaryl;
• each Rk4 and Rks are independently selected from the group consisting of H and C1-C10 alkyl;
• and
• p is selected from 1, 2, 3, 4, 5, and 6.

A composition comprising a pharmaceutical agent assembled with a lipid composition comprising an ionizable lipid, wherein the ionizable lipid has an amine head group and at least one hydrophobic tail RLipid having a structure of Formula (I):

• or a pharmaceutically acceptable salt thereof;
• wherein:
• *indicates a point of attachment to a nitrogen in the amine headgroup;
• R1 and R2 are each independently selected from the group consisting of C1-C12 alkylene, C1-C12 alkenylene, and 1- to 12-membered heteroalkylene;
• X is
• each of L3, L4, L5, and L6 is independently selected from the group consisting of a bond, O, S, and NRc;
• G is selected from the group consisting of O, S, and NRd;
• Q is selected from the group consisting of ORe, SRf, and NRgRh;
• r is selected from the group consisting of 1, 2, 3, 4, 5, and 6;
• t is selected from the group consisting of 1, 2, 3, 4, 5, and 6;
• each of Re, Rd, Rc, Rf, Rg, and Rh is independently selected from the group consisting of H, C1-C10 alkyl, 1- to 10-membered heteroalkyl, aryl, and heteroaryl;
• Y and U are each independently selected from the group consisting of a bond, O, S, NR10, and Se;
• n is 0 or 1;
• R3 and R4, are each independently selected from the group consisting of H, C1-C10 alkyl, 1- to 10-membered heteroalkyl, aryl, and heteroaryl;
• or R3 and R4 together with the atom to which they are attached to form ═O;
• R5 is selected from the group consisting of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, 1- to 20-membered heteroalkyl, 3- to 20-membered heterocycloalkyl, aryl, and heteroaryl;
• R10 is selected from the group consisting of H and C1-C5 alkyl;
• and
• the pharmaceutical agent comprises an mRNA encoding at least one therapeutic peptide for immunotherapy.