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 con...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.展开更多
基金We are grateful to Beijing Natural Science Foundation(7212212)National Natural Science Foundation of China(11875269 and 21574136)Hundred Talents Program of CAS for financial support。
文摘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.
基金supported by the National Key R&D Program of China(2021YFA1600202)the National Natural Science Foundation of China(U2032162,81972191,U1932158,and 81871085)+7 种基金Hefei Institutes of Physical Science Director’s Fund(BJPY2021B06)the Collaborative Innovation Program of Hefei Science Center of CAS(2022HSCCIP013)Anhui Provincial Natural Science Foundation(2208085J10)Hefei Municipal Natural Science Foundation(2021009)the Natural Science Foundation of Shandong Province(ZR2019LZL018)the High Magnetic Field Laboratory of Anhui Province(AHHM-FX-2021-04)the Project of China Postdoctoral Science Foundation(2019M652403)the Project of Postdoctoral Innovation of Shandong Province(202002048)。
