Nanoplatforms for biomolecule delivery to the lymph nodes haveattracted considerable interest as vectors for immunotherapy. Core−shell iron oxidenanoparticles are particularly appealing because of their potential as theranosticmagnetic resonance imaging (MRI)-trackable vehicles for biomolecule delivery. Thekey challenge for utilizing iron oxide nanoparticles in this capacity is control of theircoating shells to produce particles with predictable size. Size determines both thecarrier capacity for biomolecule display and the carrier ability to target the lymphnodes. In this study, we develop a novel coating method to produce core−shell ironoxide nanoparticles with controlled size. We utilize lipidlike molecules to stabilizeself-assembled lipid shells on the surface of iron oxide nanocrystals, allowing theformation of consistent coatings on nanocrystals of varying size (10−40 nm). Wefurther demonstrate the feasibility of leveraging the ensuing control of nanocarriersize for optimizing the carrier functionalities. Coated nanoparticles with 10 and 30nm cores supported biomolecule display at 10-fold and 200-fold higher capacitiesthan previously reported iron oxide nanoparticles, while preserving monodisperse sub-100 nm size populations. In addition,accumulation of the coated nanoparticles in the lymph nodes could be tracked by MRI and at 1 h post injection demonstratedsignificantly enhanced lymph node targeting. Notably, lymph node targeting was 9−40 folds higher than that for previouslyreported nanocarriers, likely due to the ability of these nanoparticles to robustly maintain their sub-100 nm size in vivo. Thisapproach can be broadly applicable for rational design of theranostic nanoplatforms for image-monitored immunotherapy.