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Construction of reduction-sensitive heterodimer prodrugs of doxorubicin and dihydroartemisinin self-assembled nanoparticles with antitumor activity.
- Source :
-
Colloids & Surfaces B: Biointerfaces . Sep2022, Vol. 217, pN.PAG-N.PAG. 1p. - Publication Year :
- 2022
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Abstract
- 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-SS-DHA 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 DOX-SS-DHA NPs with less cytotoxicity. [Display omitted] • A novel heterodimer prodrug (DOX-SS-DHA) was synthesized to take advantages of the combination therapy. • In vitro efficacy studies of the designed DOX-SS-DHA NPs showed enhanced tumor suppression and improved survival time. • DOX-SS-DHA NPs prepared here had better security to mice and better selectivity to the tumor sites of mice. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09277765
- Volume :
- 217
- Database :
- Academic Search Index
- Journal :
- Colloids & Surfaces B: Biointerfaces
- Publication Type :
- Academic Journal
- Accession number :
- 158727321
- Full Text :
- https://doi.org/10.1016/j.colsurfb.2022.112614