Described is a lipid nanoparticle composition that includes a macromolecule conjugated to a polymer and a targeting agent. The composition can include a therapeutic agent. The therapeutic agent can be an antisense oligonucleotide (ASO). Exemplary ASOs are targeted to a portion of a nucleic acid encoding Akt-1, and which modulates the expression of Akt-1； or targeted to a portion of a nucleic acid encoding HIF-1, and which modulates the expression of HIF-1. Also described is a lipid nanoparticle composition that includes a macromolecule conjugated to a polymer and a therapeutic agent that is an ASO such as an ASO targeted to a portion of a nucleic acid encoding Akt-1, and which modulates the expression of Akt-1 or an ASO targeted to a portion of a nucleic acid encoding HIF-1, and which modulates the expression of HIF-1. Pharmaceutical formulations, methods of making the lipid nanoparticles, and methods of using the lipid nanoparticles, for example for treating cancers, are also disclosed.
