Payload Release Profile and Anti-Cancer Stem Cell Properties of Compositionally Different Polymeric Nanoparticles Containing a Copper(II) Complex

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 1 by two compositionally different methoxy poly(ethylene glycol)-b-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 1:1 NP(15) and 4:1 NP(15), respectively, both with a 15% feed of 1. The two formulations show distinct biophysical and in vitro properties. For example, (i) 4:1 NP(15) displays a slower payload release profile than 1:1 NP(15) in physiologically relevant solutions, (ii) 4:1 NP(15) exhibits statistically greater potency towards breast CSCs than bulk breast cancer cells grown in monolayers, whereas 1:1 NP(15) is equally potent towards breast CSCs and bulk breast cancer cells, and (iii) 4:1 NP(15) shows significantly greater potency towards three-dimensionally cultured mammospheres than 1:1 NP(15). This study shows that the release profile and anti-breast CSC properties of PEG–PLGA nanoparticle formulations (containing 1) can be perturbed (and possibly controlled) by modifying the proportion of glycolic acid within the PLGA component.