Redox dual-responsive paclitaxel-doxorubicin heterodimeric prodrug self-delivery nanoaggregates for more effective breast cancer synergistic combination chemotherapy

Publication date: Available online 24 July 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Yingli Wang, Jiamei Wang, Liyuan Yang, Wei Wei, Bingjun Sun, Kexin Na, Yuxi Song, Haotian Zhang, Zhonggui He, Jin Sun, Yongjun WangAbstractA 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-PEG2K 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.Graphical AbstractWe developed a redox dual-responsive prodrug nanosystem that consisted of paclitaxel-doxorubicin heterodimeric ...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research