Mitochondrial temperature-responsive drug delivery reverses drug resistance in lung cancer
Lifo Ruan, Jun Chen, Chuanchao Du, Huiru Lu, Jiayu Zhang, Xiaomeng Cai, Rui Dou, Wenchu Lin, Zhifang Chai, Guangjun Nie, Yi Hu
Abstract
Reversal of cancer drug resistance remains a critical challenge in chemotherapy. Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer. To overcome the intrinsic limitations in conventional mitochondrial targeting strategies, we develop mitochondrial temperature-responsive drug delivery to reverse doxorubicin (DOX) resistance in lung cancer. Results demonstrate that the thermoresponsive nanocarrier can prevent DOX efflux and facilitate DOX accumulation and mitochondrial targeting in DOX-resistant tumors. As a consequence, thermoresponsive nanocarrier enhances the cytotoxicity of DOX and reverses the drug resistance in tumor-bearing mice. This work represents the first example of mitochondrial temperature-responsive drug delivery for reversing cancer drug resistance.