化疗的有效性主要受到药物抗性的阻碍，而自噬在克服这种抗性中发挥着关键作用。在这个项目中，我们开发了一种名为HTf@DOX/Qu NPs的人体转铁蛋白纳米药物，它含有诱导过度自噬的槲皮素（一种药物）和阿霉素。这种纳米药物的目的是增强线粒体自噬和与耐药癌症的搏斗。通过体外研究，我们证明了HTf@DOX/Qu NPs能够有效下调环氧合酶-2（COX-2），通过PINK1/Parkin通路过度促进线粒体自噬和随后的线粒体功能障碍。此外，HTf@DOX/Qu NPs能够上调促凋亡蛋白诱导细胞凋亡，从而有效逆转药物抗性。此外，在体内结果显示，HTf@DOX/Qu NPs在血液中循环时间延长，在肿瘤中药物积累增加，并且在药物耐药肿瘤模型中具有优越的治疗效果，优于单独化疗。本研究提出了一种通过使用转铁蛋白纳米颗粒加剧线粒体自噬的有希望的对抗多药耐药癌症的策略。本文受版权保护。版权所有，禁止转载。

The effectiveness of chemotherapy is primarily hindered by drug resistance, and autophagy plays a crucial role in overcoming this resistance. In this project, we have developed a human transferrin nanomedicine known as HTf@DOX/Qu NPs, which contains quercetin (a drug to induces excessive autophagy) and doxorubicin. The purpose of this nanomedicine is to enhance mitophagy and combating drug-resistant cancer. Through in vitro studies, we have demonstrated that HTf@DOX/Qu NPs can effectively downregulate cyclooxygenase-2 (COX-2), leading to an excessive promotion of mitophagy and subsequent mitochondrial dysfunction via the PINK1/Parkin axis. Additionally, HTf@DOX/Qu NPs can upregulate proapoptotic proteins to induce cellular apoptosis, thereby effectively reversing drug resistance. Furthermore, in vivo results have shown that HTf@DOX/Qu NPs exhibit prolonged circulation in the bloodstream, enhanced drug accumulation in tumors, and superior therapeutic efficacy compared to individual chemotherapy in a drug-resistant tumor model. This study presents a promising strategy for combating multidrug-resistant cancers by exacerbating mitophagy through the use of transferrin nanoparticles. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.