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The present study highlights the importance of understanding the structural changes of micelles induced by drug loading on their physico-chemical properties.Ablock copolymer with attached fructose,whichinteracts with GLUT5 receptor,w as used and conjugated with al ow and ah igh amount of platinum drugs.A gainst expectations,t he lowloading micelle,despite having aless defined morphology and larger nanoparticle sizea ccording to TEM, displays higher cellular uptake and higher toxicity.This behaviour can only be understood when elucidating additional information on the structure of micelles.Extensive solid-state NMR measurements were therefore employed to reveal that the drug loading affected swelling and mobility of core and shell of the micelle. The results obtained from solid-state NMR spectroscopycould explain all the observations on this system. In summary,solidstate NMR spectroscopyisa ne xcellent tool to understand the effects of drug loading on the behavior of micelles. Polymermicellesarewidelyappliedasnanocarriersfordrug delivery.[1] Shape,size,and surface functionalization [2] are the primary design factors that are considered for controlling the nanoparticle-cell interactions.Self-assembled polymer nanoparticles (PNs) used as delivery vehicles for anti-cancer drugs overcome some of the drawbacks exhibited by free anticancer drugs such as poor/non-specificity,l ow solubility,t he requirement for high drug concentration within the tissue,and toxicity limited dosage.[3] PNs can improve drug stability, solubility,b iodistribution and specificity,p rolong circulating half-life,exert an enhanced permeation and retention (EPR) effect, and enable controlled triggered release of the drug payload. [4] Theu pshot is that PNs allow the use of ar educed drug dose and therefore minimize the debilitating side effects of anti-cancer drugs.Arange of nanoparticles for drug delivery purposes are available,including highly popular micelles.[5] It is implicitly assumed that polymeric micelles have welldefined core-shell morphology and their bioactivity and cellular uptake are primarily dependent on external parameters such as nanoparticle size,s hape,a nd surface chemistry. [2,6] Thee ffect of drug loading on the morphology and molecular dynamics of the micellar drug carrier,and thus the biological activity,has so far been neglected in the literature, although afew reports suggest that drug loading can enhance the stability of the micelle against disassembly. [7] There is also ac ommon assumption that researchers need to strive for ah igh drug loading to yield the best possible efficacy. However,l ittle attention is given to the effect of the amount of drug loading on the physico-chemical changes in the core and shell of nanoparticles.Herein, we apply an analytical tool, solid-state NMR spectroscopy,t oh elp understand how drug loading and the amount of drug can influence the properties of the nanoparticle,w hich can furthermore affect their behavior in ab iological setting.K nowledge of the internal structure ...