期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 26, 期 69, 页码 16318-16327出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202001579
关键词
apoptosis; cancer; drug delivery; nanoparticles; targeting
资金
- Generalitat Valenciana [ACIF/2017/072, PROMETEO/2018/024, PROMETEO/2019/065]
- Spanish Government [FPU15/02753, RTI2018-100910-B-C41, SAF2017-84689-R-B]
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. In the last years, navitoclax has emerged as a possible treatment for TNBC. Nevertheless, rapid navitoclax resistance onset has been observed thorough Mcl-1 overexpression. As a strategy to overcome Mcl-1-mediated resistance, herein we present a controlled drug co-delivery system based on mesoporous silica nanoparticles (MSNs) targeted to TNBC cells. The nanocarrier is loaded with navitoclax and the Mcl-1 inhibitor S63845 and capped with a MUC1-targeting aptamer (apMUC1-MSNs(Nav/S63845)). The apMUC1-capped nanoparticles effectively target TNBC cell lines and successfully induce apoptosis, overcoming navitoclax resistance. Moreover, navitoclax encapsulation protects platelets against apoptosis. These results point apMUC1-gated MSNs as suitable BH3 mimetics nanocarriers in the targeted treatment of MUC1-expressing TNBC.
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