Preparation of CPT-PD was achieved via a one-step coupling of oxidized lipid PAzPC (1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine) with CPT (Supplementary methods). A VLA-4 antagonist based on the highly selective peptidomimetic, LLP2A (19 (link)), was synthesized and coupled to a polyethylene glycol–phosphatidyethanolamine anchor as detailed in Supplementary methods (Fig 1A, Suppl 1D-E). Therapeutic mixed micelles were prepared by microfluidization. The surfactant co-mixture of nanoparticles included phosphatidylcholine (Lipoid, Ludwigshafen, Germany) and 0.18 mol% of VLA4-PEG-PE. The peptidomimetic αvβ3-integrin homing ligand was a gift from Kereos, Inc. (St. Louis, MO) and incorporated into control micellar nanoparticles as previously described (21 (link)). For particle uptake assays, DiI (1 mol%, Thermo Fisher Scientific Inc, Waltham, MA) was incorporated. V-CP included 4 mol% of CPT-PD, and was replaced in “No-Drug” (ND) nanoparticles by phosphatidylcholine. Dynamic light scattering was performed with ZetaPlus (Brookhaven Instruments Corporation) on every batch: particle size (average 18.2 ± 3.0), polydispersity (0.24), and electrophoretic zeta potential (−3.1 mV). Data from several batches V-NP illustrated high batch-to-batch reproducibility and long-term shelf-life stability (~1 year at 4°C) (Suppl Fig 1F).