期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 217, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.colsurfb.2022.112614
关键词
Doxorubicin; Dihydroartemisinin; Heterodimer prodrugs; Reduction-sensitive; Self-assembled nanoparticles
资金
- National Natural Science Foundation of China [82173767, 81803470]
- Shanxi Scholarship Council of China [2021-089]
- Applied Basic Research Project of Shanxi Province [20210302123310]
- Science and Technology Innovation projects of Shanxi Platform Base and Talent Special Project [201805D211002]
- Postgraduate Innovation Project of Shanxi Province [2021Y420]
This study designed and prepared reduction-responsive nanoparticles containing Doxorubicin and Dihydroartemisinin, which exhibited better antitumor activity and less cytotoxicity compared to traditional chemotherapeutic drugs.
Doxorubicin (DOX) is used as a first-line chemotherapeutic drug, whereas dihydroartemisinin (DHA) also shows a certain degree of antitumor activity. Disulfide bonds (-SS-) in prodrug molecules can be degraded in highly reducing environments. Thus, heterodimer prodrugs of DOX and DHA linked by a disulfide bond was designed and subsequently prepared as reduction-responsive self-assembled nanoparticles (DOX-SS-DHA NPs). In an in vitro release study, DOX-SS-DHA NPs exhibited reduction-responsive activity. Upon cellular evaluation, DOX-SSDHA NPs were found to have better selectivity toward tumor cells and less cytotoxicity to normal cells. Compared to free DiR, DOX-SS-DHA NPs showed improved accumulation at the tumor site and even had a longer clearance half-life. More importantly, DOX-SS-DHA NPs possessed a much higher tumor inhibition efficacy than DOX-sol and MIX-sol in 4T1 tumor-bearing mice. Our results suggested the superior antitumor efficacy of DOXSS-DHA NPs with less cytotoxicity.
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