School of Chemistry, University of Leicester, Leicester LE1 7RH, UK.
Molecules. 2023 Mar 9;28(6):2506. doi: 10.3390/molecules28062506.
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 by two compositionally different methoxy poly(ethylene glycol)--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 and , respectively, both with a 15% feed of . The two formulations show distinct biophysical and in vitro properties. For example, (i) displays a slower payload release profile than in physiologically relevant solutions, (ii) exhibits statistically greater potency towards breast CSCs than bulk breast cancer cells grown in monolayers, whereas is equally potent towards breast CSCs and bulk breast cancer cells, and (iii) shows significantly greater potency towards three-dimensionally cultured mammospheres than . This study shows that the release profile and anti-breast CSC properties of PEG-PLGA nanoparticle formulations (containing ) can be perturbed (and possibly controlled) by modifying the proportion of glycolic acid within the PLGA component.
癌症干细胞（CSCs）与肿瘤复发和转移有关，是癌症相关死亡的主要原因。将聚合物纳米粒子作为药物输送系统靶向 CSCs 的应用尚未得到充分探索。在这里，我们报告了将一种 CSC 有效铜（II）配合物封装在两种组成不同的甲氧基聚（乙二醇）-聚（D，L-乳酸-共-乙醇酸）（PEG-PLGA）共聚物中。具体而言，我们使用 PEG-PLGA（5000:10,000 Da，1:1 LA:GA）和 PEG-PLGA（5000:10,000 Da，4:1 LA:GA）聚合物分别制备了球形纳米粒子制剂和，其中分别含有 15%的。这两种制剂表现出明显不同的物理化学性质和体外特性。例如，（i）在生理相关溶液中，释放出的有效载荷比 慢，（ii）对乳腺癌 CSCs 的效力明显大于单层培养的乳腺癌细胞，而对乳腺癌 CSCs 和乳腺癌细胞的效力相等，（iii）对三维培养的类乳腺球体的效力明显大于。本研究表明，通过改变 PLGA 成分中乙醇酸的比例，可以改变（并可能控制）PEG-PLGA 纳米粒子制剂（含有 ）的释放特性和抗乳腺癌 CSC 特性。
