Fighting Against Drug-resistant Tumor by The Induction of Excessive Mitophagy with Transferrin Nanomedicine.
Yuanxiang YuSijin ChenYupeng WangDongfang ZhouDehua WuPublished in: Macromolecular bioscience (2023)
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.
Keyphrases
- drug resistant
- multidrug resistant
- gram negative
- acinetobacter baumannii
- endoplasmic reticulum stress
- cancer therapy
- cell death
- klebsiella pneumoniae
- weight gain
- oxidative stress
- nlrp inflammasome
- oxide nanoparticles
- signaling pathway
- endothelial cells
- papillary thyroid
- randomized controlled trial
- locally advanced
- cell cycle arrest
- drug delivery
- systematic review
- quality improvement
- body mass index
- squamous cell
- squamous cell carcinoma
- weight loss
- adverse drug
- nitric oxide
- childhood cancer
- emergency department
- lymph node metastasis
- nitric oxide synthase
- pluripotent stem cells
- pi k akt
- walled carbon nanotubes