Cargo Nile red Morphine-H+ Compartment DG DH -TDS DG DH -TDS Glu Outer Shell 17.0 17.1 -0.1 15.2 15.3 -0.1 Inner Shell 14.9 15.0 -0.1 18.8 19.0 -0.3 Core 18.8 19.0 -0.2 15.6 15.8 -0.1 Asp Outer Shell 15.9 16.0 -0.1 13.4 13.4 -0.1 Inner Shell 12.5 12.6 -0.9 18.9 19.2 -0.2 Core 16.1 16.3 -0.2 14.7 14.8 -0.1

Table 2: Energy differences (kJ/mol) for guest molecules in CMS nanotransporters with glutamate (Glu) and aspartate (Asp) outer shell. Lower differences in free energy (ΔG), inner energy (H), and entropy (TΔS) indicate higher loading in the compartments of the optimized CMS nanotransporters.