期刊
BIOCONJUGATE CHEMISTRY
卷 31, 期 8, 页码 2008-2020出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.0c00364
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资金
- National Natural Science Foundation of China [81902670, 81971622, 81671696, 51703141]
- Sichuan Key Research and Development Project from Sichuan Provincial Science and Technology Department [2019YFS0424, 2019YFS0036, 2019YFS0219]
- Post-Doctor Research Project, West China Hospital, Sichuan University [2018HXBH077]
Paclitaxel (PTX) resistance in most epithelial ovarian cancers (EOCs) with increasing membrane expression of mucin 16 (MUC16) is mediated by the Toll-like receptor-myeloid differentiation factor 2/myeloid differentiation factor 88 (TLR4-MD2/MyD88) signaling pathway. 6-Shogaol (6S), an alpha,beta-unsaturated carbonyl compound with lipophilic property, can block PTX-induced formation of the TLR4-MD2 complex that activates the MyD88/NF-kappa B signaling pathway. Herein, to improve the effectiveness of 6S, augment the sensibility of PTX, and enhance the targeting ability of PTX-resistant cancer therapies, we report a class of 6S-loaded phase transition nanobubbles conjugated with the MUC16 antibody (6S@NBs-MUC16A), which can enhance the sensitivity of PTX to EOC cells through ultrasound-controlled targeted-delivery of 6S. The 6S@NB-MUC16A could enhance the targeting efficiency and organizational distribution of 6S in MyD88(+) EOC area, and the 1 MHz ultrasound can be used as an initiator to trigger the explosion of nanobubbles and promote the 6S release. Furthermore, in vivo assessment results indicate that ultrasound-augmented 6S@NB-MUC16A can significantly improve the response of EOC to PTX and the inhibition ratio of tumor growth compared to the control-treated with PTX alone, and exhibit less toxicity to the critical organs. The ultrasound-augmented 6S@NB-MUC16A with less cytotoxicity could be a potentially useful nanosystem to surmount PTX resistance in EOC, which provides potential possibilities for the applications in the biological field.
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