众所周知，高谷胱甘肽的产生是许多癌细胞在升高的氧化应激下生存的防御机制之一。通过明确靶向这些癌细胞中的谷胱甘肽并降低其水平，可以加剧氧化应激，最终引发细胞凋亡或程序性细胞死亡。在此，我们开发了一种新方法，通过创建马来酰亚胺功能化的聚己内酯聚合物，特别是使用 2,3-二碘马来酰亚胺功能来降低癌细胞中谷胱甘肽的水平。由于其可生物降解和生物相容性特性，选择聚己内酯来缀合 2,3-二碘马来酰亚胺官能团。使用PEG作为大分子引发剂合成了两亲性嵌段共聚物，以制备相应的聚合物胶束。所得的 2,3-二碘马来酰亚胺缀合的聚己内酯胶束即使在低浓度（0.01 mg mL-1）下也能有效猝灭谷胱甘肽。此外，我们还在这些胶束中装载了抗癌药物阿霉素 (DOX)，该药物表现出 pH 依赖性药物释放。我们获得了 3.5% 的胶束负载能力 (LC)，这是功能性 PCL 胶束中报道的最高 LC 之一。此外，增强的 LC 不会影响其释放曲线。细胞毒性实验表明，空胶束和负载 DOX 的胶束可抑制癌细胞生长，其中负载 DOX 的胶束表现出最高的细胞毒性。该聚合物淬灭细胞内 GSH 的能力也得到了证实。这种将马来酰亚胺附着到聚己内酯聚合物上的方法有望消除癌细胞中升高的谷胱甘肽水平，从而有可能提高癌症治疗效果。该期刊版权所有©英国皇家化学学会。

High glutathione production is known to be one of the defense mechanisms by which many cancer cells survive elevated oxidative stress. By explicitly targeting glutathione in these cancer cells and diminishing its levels, oxidative stress can be intensified, ultimately triggering apoptosis or programmed cell death. Herein, we developed a novel approach by creating maleimide-functionalized polycaprolactone polymers, specifically using 2,3-diiodomaleimide functionality to reduce the level of glutathione in cancer cells. Polycaprolactone was chosen to conjugate the 2,3-diiodomaleimide functionality due to its biodegradable and biocompatible properties. The amphiphilic block copolymer was synthesized using PEG as a macroinitiator to make corresponding polymeric micelles. The resulting 2,3-diiodomaleimide-conjugated polycaprolactone micelles effectively quenched glutathione, even at low concentrations (0.01 mg mL-1). Furthermore, we loaded these micelles with the anticancer drug doxorubicin (DOX), which exhibited pH-dependent drug release. We obtained a loading capacity (LC) of 3.5% for the micelles, one of the highest LC reported among functional PCL-based micelles. Moreover, the enhanced LC doesn't affect their release profile. Cytotoxicity experiments demonstrated that empty and DOX-loaded micelles inhibited cancer cell growth, with the DOX-loaded micelles displaying the highest cytotoxicity. The ability of the polymer to quench intracellular GSH was also confirmed. This approach of attaching maleimide to polycaprolactone polymers shows promise in depleting elevated glutathione levels in cancer cells, potentially improving cancer treatment efficacy.This journal is © The Royal Society of Chemistry.