Journal
BIOACTIVE MATERIALS
Volume 13, Issue -, Pages 191-199Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.10.045
Keywords
Mitochondrial temperature; Thermoresponsive; Drug delivery; Drug resistance; Nanomedicines
Funding
- Beijing Natural Science Foundation [7212212]
- National Natural Science Foundation of China [11875269, 21574136]
- Hundred Talents Program of CAS
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The use of mitochondrial temperature-responsive drug delivery system can prevent drug efflux, facilitate drug accumulation and mitochondrial targeting in drug-resistant tumors. This technology enhances drug toxicity and reverses drug resistance, representing a significant advancement in combating cancer drug resistance.
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 nano carrier 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.
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