*2.1. Synthesis and Characterization of SLPs*

The synthesis of SLPs was made by a modified melt emulsification method (Figure S1) as previously described [29]. Briefly, 100 mg of carnauba wax (T1 E00018; Koster Keunen, Watertown, CT, USA) was mixed with (i) a total of 30 mg of iron oxide (Fe3O4) nanoparticles, prepared following the coprecipitation method [30], with 13.02 ± 0.24 nm of diameter

in a chloroform solution (99.5%, C2432; Sigma, St. Louis, MO, USA); (ii) 250 µL of 3,30 dioctadecyloxacarbocyanine perchlorate (DiO) (D275; Invitrogen, Waltham, MA, USA) at 1 mg/mL in chloroform; and (iii) DOX (A14403; Adooq Bioscience, Irvine, CA, USA) (20 mg/mL). This mixture was heated until complete wax melting and chloroform (C2432; Sigma, Darmstadt, Germany) evaporation was achieved. Then, 2.25 mL of Milli-Q water and 250 µL of a 50 mg/mL water solution of Tween80 (P4780; Sigma, Darmstadt, Germany) were added to the vial. The sample was ultrasonicated (Branson 250; Emerson, St. Louis, MO, USA) at 25% power for 2 min at 20 s working intervals. The vial was cooled by a digital sonifier by immersion in ice to solidify the lipid particles. Finally, the formulation was centrifuged (Hettich Zentrifugen Universal 320, Tuttlingen, Germany) (3000 rpm, 10 min) and the supernatant was freeze-dried in the presence of sucrose (0.9% *w*/*w*) as a cryoprotectant.

Hydrodynamic diameters, ζ potential values and the polydispersity index of the SLPs were measured using dynamic light scattering (DLS) (Horiba Scientific SZ-100 instrument; Kyoto, Japan), and morphology was observed through transmission electron microscopy (TEM) images using a JEOL JEM-2100 (Tokyo, Japan) microscope at an accelerating voltage of 200 kV (Figure S2). The amount of DOX loaded from the SLPs was determined by high-performance liquid chromatography (UHPLC; Agilent 1290 Infinity II LC System; Santa Clara, CA, USA) using a gradient of water:acetonitrile (from 100% to 25:75%) and an Aeris 1.7 µm peptide XB-C18 column (Phenomenex; Torrance, CA, USA). Graphics were designed by BioRender.com.
