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

doi:10.1016/j.bioactmat.2021.10.045

Mitochondrial temperature-responsive drug delivery reverses drug resistance in lung cancer

Bioact Mater. 2021 Nov 4:13:191-199. doi: 10.1016/j.bioactmat.2021.10.045. eCollection 2022 Jul.

Authors

Lifo Ruan^{1

2}, Jun Chen^{1

2}, Chuanchao Du³, Huiru Lu¹, Jiayu Zhang¹, Xiaomeng Cai^{1

2}, Rui Dou^{1

2}, Wenchu Lin^{4

5}, Zhifang Chai^{1

2}, Guangjun Nie^{2

6}, Yi Hu^{1

2}

Affiliations

¹ CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, 100049, PR China.
² University of Chinese Academy of Sciences, Beijing, 100049, PR China.
³ Peking University Third Hospital, Beijing, 100191, PR China.
⁴ High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, Anhui, PR China.
⁵ University of Science and Technology of China, Hefei, 230026, Anhui, PR China.
⁶ CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, PR China.

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.

Keywords: Drug delivery; Drug resistance; Mitochondrial temperature; Nanomedicines; Thermoresponsive.