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Cancer stem cells (CSCs) are linked to tumour relapse and metastasis, the main reason for cancer-related deaths. The application of polymeric nanoparticles as drug delivery systems to target CSCs is relatively unexplored. Here, we report the encapsulation of a CSC-potent copper(II) complex <b>1</b> by two compositionally different methoxy poly(ethylene glycol)-<i>b</i>-poly(D,L-lactic-co-glycolic) acid (PEG–PLGA) copolymers. Specifically, we used PEG–PLGA (5000:10,000 Da, 1:1 LA:GA) and PEG–PLGA (5000:10,000 Da, 4:1 LA:GA) polymers to prepare spherical nanoparticle formulations <b>1:1 NP¹⁵</b> and <b>4:1 NP¹⁵</b>, respectively, both with a 15% feed of <b>1</b>. The two formulations show distinct biophysical and in vitro properties. For example, (i) <b>4:1 NP¹⁵</b> displays a slower payload release profile than <b>1:1 NP¹⁵</b> in physiologically relevant solutions, (ii) <b>4:1 NP¹⁵</b> exhibits statistically greater potency towards breast CSCs than bulk breast cancer cells grown in monolayers, whereas <b>1:1 NP¹⁵</b> is equally potent towards breast CSCs and bulk breast cancer cells, and (iii) <b>4:1 NP¹⁵</b> shows significantly greater potency towards three-dimensionally cultured mammospheres than <b>1:1 NP¹⁵</b>. This study shows that the release profile and anti-breast CSC properties of PEG–PLGA nanoparticle formulations (containing <b>1</b>) can be perturbed (and possibly controlled) by modifying the proportion of glycolic acid within the PLGA component.