Carboplatin, administered as a single drug or in combination with paclitaxel, is the standard chemotherapy treatment for patients with ovarian cancer (OVCA). Recent evidence suggests that miRNAs associated with small extracellular vesicles (sEVs) participate in the development of chemoresistance. We studied the effect of carboplatin in a heterogeneity population of OVCA cells and their derived sEVs to identify mechanisms associated with chemoresistance. sEVs were quantified using an engineered superparamagnetic material, gold-loaded ferric oxide nanotubes and a screen-printed electrode. miR-21-3p, miR-21-5p, and miR-891-5p are enriched in sEVs, and they contribute to carboplatin resistance in OVCA. Using a quantitative MS/MS, miR-21-5p activates glycolysis and increases the expression of ATP-binding cassette family and a detoxification enzyme. miR-21-3p and miR-891-5p increase the expression of proteins involved in DNA repair mechanisms. Interestingly, the levels of miR-891-5p within sEVs are significantly higher in patients at risk of ovarian cancer relapse. Identification of miRNAs in sEVs also provides the opportunity to track them in biological fluids to potentially determine patient response to chemotherapy.

卡铂作为单一药物或与紫杉醇联合给药，是卵巢癌（OVCA）患者的标准化学疗法。最近的证据表明，与小细胞外囊泡（sEVs）相关的miRNA参与化学抗性的发展。我们研究了卡铂在OVCA细胞及其衍生的sEVs的异质性群体中的作用，以鉴定与化学耐药性相关的机制。使用工程超顺磁性材料，载金的三氧化二铁纳米管和丝网印刷电极对sEV进行定量。miR-21-3p，miR-21-5p和miR-891-5p富含sEV，并且它们有助于OVCA中的卡铂耐药性。使用定量MS / MS，miR-21-5p激活糖酵解并增加ATP结合盒家族和解毒酶的表达。miR-21-3p和miR-891-5p可增加参与DNA修复机制的蛋白质的表达。有趣的是，在具有卵巢癌复发风险的患者中，sEV中的miR-891-5p水平显着更高。sEV中miRNA的鉴定也提供了在生物液体中追踪它们的机会，从而有可能确定患者对化学疗法的反应。