LDL particles are high-capacity nanocarriers with precisely controlled size and are naturally biocompatible, biodegradable, and nonimmunogenic. However, their utilities as drug carriers are limited by the narrow purview of LDL receptor-positive tumors. Here, we synthsized a ligand-conjugated, NIR-labeled LDL that enables the first in vivo demonstration of rerouting LDL from LDL receptors to selected alternate receptors, thus drastically expanding the range of using LDL particles as nanocarriers for in vivo cancer imaging and treatment.