| Autor: |
Wang, Yingli, Wang, Jiamei, Yang, Liyuan, Wei, Wei, Sun, Bingjun, Na, Kexin, Song, Yuxi, Zhang, Haotian, He, Zhonggui, Sun, Jin, Wang, Yongjun |
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| Zdroj: |
Nanomedicine: Nanotechnology, Biology & Medicine; Oct2019, Vol. 21, pN.PAG-N.PAG, 1p |
| Abstrakt: |
A single nanodrug delivery system for combined delivery of paclitaxel and doxorubicin that integrates high co-loading efficiency, synchronous co-delivery of combined drugs, controllable drug release, and maintains the drug combination at fixed synergistic ratios has been proven to be challenging. Here, we report a redox dual-responsive prodrug nanosystem consisting of a paclitaxel-doxorubicin heterodimeric prodrug with a thioether bond linkage to effectively co-deliver two therapeutic drugs. The heterodimeric prodrug could self-assemble into uniform nanoaggregates containing DSPE-PEG 2K with a precise drug co-loading ratio in water, and possessed a high co-loading content. We demonstrated that this nanosystem provided strong synergistic effects in MCF-7 and 4 T1 cells. In vivo , this nanosystem results in a long blood circulation, high accumulation in the tumor, and significant inhibition of tumor growth in BALB/c mice bearing 4 T1 tumors. Such a simple, safe, and efficient heterodimeric prodrug nanosystem exhibits great potential for clinical translation in future combination chemotherapy treatments. We developed a redox dual-responsive prodrug nanosystem that consisted of paclitaxel-doxorubicin heterodimeric prodrug with thioether bond linkage to effectively co-deliver paclitaxel and doxorubicin to cancer cells. The prodrug nanoaggregates extravasate through the leaky tumor vasculature. The thioether bonds of the nanoaggregates are cleaved under the intracellular high GSH and ROS level, triggering the rapid release of PTX and DOX. Unlabelled Image [ABSTRACT FROM AUTHOR] |
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