阿霉素 (DOX) 是一种用于治疗肝细胞癌 (HCC) 的化疗药物，但其疗效可能会因癌细胞化疗耐药性而大大减弱。信号转导子和转录激活子 3 (STAT3) 与一系列癌症（例如 HCC）的耐药性有关，抑制 STAT3 可以逆转癌细胞对化疗药物的耐药性。在本研究中，通过使用白花丹素 (PLB) 阻断 STAT3 提供了一种提高 DOX 效率的组合方案。本研究生产了一种由聚乙二醇和氨基乙基茴香酰胺修饰的聚乳酸-乙醇酸共聚物，希望生成用于共同递送 DOX 和 PLB 的纳米颗粒。由此产生的复合制剂抑制了 STAT3 活性并实现了协同化疗，从而抑制了皮下 DOX 耐药性 HCC 小鼠的肿瘤，且不引起任何毒性。本研究揭示了 DOX 和 PLB 的协同作用，并展示了一种治疗 HCC 的有前途的组合方法。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Doxorubicin (DOX) is a chemotherapy drug used for hepatocellular carcinoma (HCC) treatment, but its effectiveness can be dramatically dampened by cancer cell chemoresistance. Signal transducer and activator of transcription 3 (STAT3) is implicated with drug resistance in a range of cancers (e.g., HCC), and the STAT3 inhibition can reverse the resistance of cancer cells to chemotherapeutic drugs. In the present study, a combination regimen to improve the efficiency of DOX was provided via the STAT3 blockade using plumbagin (PLB). A poly(lactic-co-glycolic acid) decorated by polyethylene glycol and aminoethyl anisamide was produced in the present study with the hope of generating the nanoparticles for co-delivery of DOX and PLB. The resulting co-formulation suppressed the STAT3 activity and achieved the synergistic chemotherapy, which led to tumor inhibition in the mice with subcutaneous DOX-resistant HCC, without causing any toxicity. The present study reveals the synergism of DOX and PLB, and demonstrates a promising combinatorial approach for treating HCC.Copyright © 2024 Elsevier B.V. All rights reserved.